ES2374954T3

ES2374954T3 - GENETIC VARIATIONS ASSOCIATED WITH TUMORS.

Info

Publication number: ES2374954T3
Application number: ES07871494T
Authority: ES
Inventors: Somasekar Seshagiri; Brock Peters; Zhengyan Kan
Original assignee: Genentech Inc
Current assignee: Genentech Inc
Priority date: 2006-11-16
Filing date: 2007-11-15
Publication date: 2012-02-23
Anticipated expiration: 2027-11-15
Also published as: AU2007319214B2; CA2667851A1; AU2007319214A1; ATE527385T1; WO2008061213A3; EP2082064A2; EP2082064B1; WO2008061213A2; US20100092965A1; JP2010509922A

Abstract

Nucleotide and amino acid variations associated with tumors are provided. Methods for detecting variations and for diagnosing and treating tumors are provided.

Description

Variaciones genéticas asociadas con tumores Genetic variations associated with tumors

CAMPO DE LA INVENCIÓN FIELD OF THE INVENTION

[0001] La presente invención se refiere en general a variaciones genéticas asociadas con tumores. [0001] The present invention relates generally to genetic variations associated with tumors.

ANTECEDENTES BACKGROUND

[0002] Los cánceres pueden surgir cuando las células acumulan mutaciones somáticas que finalmente confieren una ventaja de crecimiento. Las mutaciones somáticas incluyen, por ejemplo, sustituciones de bases de nucleótidos, deleciones, inserciones, amplificaciones y redisposiciones. La identificación de mutaciones somáticas que aparecen en el cáncer proporciona una información valiosa con respecto al desarrollo del cáncer. Dicha información también es útil para la identificación de marcadores de diagnóstico y dianas terapéuticas en el cáncer (véase, por ejemplo, Bamford et al. (2004) British Journal of Cancer 91:355-358.) De este modo, existe una necesidad continua para identificar mutaciones somáticas que aparecen en el cáncer. [0002] Cancers can arise when cells accumulate somatic mutations that ultimately confer a growth advantage. Somatic mutations include, for example, nucleotide base substitutions, deletions, insertions, amplifications and redispositions. The identification of somatic mutations that appear in cancer provides valuable information regarding cancer development. Such information is also useful for the identification of diagnostic markers and therapeutic targets in cancer (see, for example, Bamford et al. (2004) British Journal of Cancer 91: 355-358.) Thus, there is a continuing need to identify somatic mutations that appear in cancer.

[0003] Las variaciones en la línea germinal, o polimorfismos, son variaciones heredables que están presentes en el genoma de un organismo. Los polimorfismos incluyen polimorfismos de longitud del fragmento de restricción, repeticiones en tándem cortos (stirs) y polimorfismos de nucleótidos únicos (SNP). Las variaciones en la línea germinal pueden estar asociadas con la susceptibilidad para ciertas enfermedades, incluyendo cáncer. (Véase, por ejemplo, Vierimaa et al. (2006) Science 312:1228-1230; Landi et al. (2006) Science 313:521-522; Zhu et al. (2004) Cancer Research 64:2251-2257.) De este modo, existe una necesidad continua de identificar polimorfismos asociados con el cáncer. [0003] Germline variations, or polymorphisms, are inheritable variations that are present in the genome of an organism. Polymorphisms include restriction fragment length polymorphisms, short tandem repeats (stirs) and single nucleotide polymorphisms (SNPs). Germline variations may be associated with susceptibility to certain diseases, including cancer. (See, for example, Vierimaa et al. (2006) Science 312: 1228-1230; Landi et al. (2006) Science 313: 521-522; Zhu et al. (2004) Cancer Research 64: 2251-2257.) Thus, there is a continuing need to identify polymorphisms associated with cancer.

[0004] La identificación de variaciones asociadas con el cáncer se ha demostrado como valiosa en disposiciones clínicas, por ejemplo, en la diferenciación de poblaciones de pacientes que son sensibles a una terapia particular. (Véase por ejemplo, Lynch et al. (2004) N. Engl.J. Med. 350:2129-2139; O’Hare (2004) Blood 104:2532-2539). [0004] The identification of variations associated with cancer has proven valuable in clinical arrangements, for example, in the differentiation of patient populations that are sensitive to a particular therapy. (See for example, Lynch et al. (2004) N. Engl.J. Med. 350: 2129-2139; O'Hare (2004) Blood 104: 2532-2539).

[0005] La invención aquí descrita cumple las necesidades descritas anteriormente y proporciona otras ventajas. [0005] The invention described herein meets the needs described above and provides other advantages.

DESCRIPCIÓN RESUMIDA SUMMARY DESCRIPTION

[0006] La invención se define en las reivindicaciones. Los métodos de la invención se basan, en parte, en el descubrimiento de nuevas variaciones en polinucleótidos derivados de muestras de tumores. [0006] The invention is defined in the claims. The methods of the invention are based, in part, on the discovery of new variations in polynucleotides derived from tumor samples.

[0007] En un aspecto, se proporciona un polinucleótido aislado, en el que el polinucleótido aislado comprende (a) un polinucleótido PRO o un fragmento del mismo que tiene por lo menos aproximadamente 10 nucleótidos de longitud, donde el polinucleótido PRO o fragmento del mismo comprende una variación de nucleótido en una posición de nucleótido seleccionada de las figuras 1-3, o (b) el complemente de (a). En una realización, la variación de nucleótido tiene lugar en las SEC ID NOs: 1-37. En otra realización, la variación de nucleótido es un cambio de nucleótido seleccionado de las figuras 1-3. En otra realización, el polinucleótido aislado es un cebador. En otra realización, el polinucleótido aislado es un oligonucleótido. [0007] In one aspect, an isolated polynucleotide is provided, in which the isolated polynucleotide comprises (a) a PRO polynucleotide or a fragment thereof that is at least about 10 nucleotides in length, wherein the PRO polynucleotide or fragment thereof it comprises a nucleotide variation in a nucleotide position selected from Figures 1-3, or (b) the complement of (a). In one embodiment, the nucleotide variation takes place in SEQ ID NOs: 1-37. In another embodiment, the nucleotide variation is a nucleotide change selected from Figures 1-3. In another embodiment, the isolated polynucleotide is a primer. In another embodiment, the isolated polynucleotide is an oligonucleotide.

[0008] En otro aspecto, se proporciona un oligonucleótido que es (a) un oligonucleótido específico de alelo que se hibrida a una región de un polinucleótido PRO que comprende una variación de nucleótido en una posición de nucleótido seleccionada de las figuras 1-3, o (b) el complemento de (a). En una realización, la variación de nucleótido es un cambio de nucleótido seleccionado de las figuras 1-3. En otra realización, el oligonucleótido específico de alelo es un cebador específico de alelo. En otra realización, se proporciona un kit que comprende el oligonucleótido y por lo menos una enzima. En una de dichas realizaciones, el por lo menos una enzima es una polimerasa. En otra de dichas realizaciones, el por lo menos una enzima es una ligasa. En una realización adicional, se proporciona un microarray que comprende el oligonucleótido. [0008] In another aspect, an oligonucleotide is provided which is (a) an allele-specific oligonucleotide that hybridizes to a region of a PRO polynucleotide comprising a nucleotide variation at a selected nucleotide position of Figures 1-3, or (b) the complement of (a). In one embodiment, the nucleotide variation is a nucleotide change selected from Figures 1-3. In another embodiment, the allele specific oligonucleotide is an allele specific primer. In another embodiment, a kit comprising the oligonucleotide and at least one enzyme is provided. In one of said embodiments, the at least one enzyme is a polymerase. In another of said embodiments, the at least one enzyme is a ligase. In a further embodiment, a microarray comprising the oligonucleotide is provided.

[0009] En otro aspecto, se proporciona un método de detección de la ausencia o presencia de una variación de nucleótido en una posición de nucleótido seleccionada de las figuras 1-3, comprendiendo el método (a) poner en contacto el ácido nucleico sospechoso de comprender la variación de nucleótido con un oligonucleótido específico de alelo que es específico para la variación de nucleótido bajo condiciones adecuadas para la hibridación del oligonucleótido específico de alelo al ácido nucleico; y (b) detectar la ausencia o presencia de hibridación específica de alelo. En una realización, la variación de nucleótido es un cambio de nucleótido seleccionado de las figuras 1-3. En otra realización, la variación de nucleótido es una mutación somática. En otra realización, la variación de nucleótido es un polimorfismo en la línea germinal. [0009] In another aspect, there is provided a method of detecting the absence or presence of a nucleotide variation in a selected nucleotide position of Figures 1-3, the method comprising (a) contacting the suspected nucleic acid of comprising nucleotide variation with an allele specific oligonucleotide that is specific for nucleotide variation under conditions suitable for hybridization of the allele specific oligonucleotide to the nucleic acid; and (b) detect the absence or presence of allele specific hybridization. In one embodiment, the nucleotide variation is a nucleotide change selected from Figures 1-3. In another embodiment, the nucleotide variation is a somatic mutation. In another embodiment, the nucleotide variation is a germline polymorphism.

[0010] En otro aspecto, se proporciona un método de amplificación de ácido nucleico que comprende una variación de nucleótido en una posición de nucleótido seleccionada de las figuras 1-3, comprendiendo el método (a) poner en contacto el ácido nucleico con un cebador que se hibrida al ácido nucleico en una secuencia 3’ de la variación de nucleótido, y (b) extender el cebador para generar un producto de amplificación que comprende la variación de nucleótido. En una realización, la variación de nucleótido es un cambio de nucleótido seleccionado de las figuras 1[0010] In another aspect, a method of nucleic acid amplification is provided comprising a nucleotide variation at a selected nucleotide position of Figures 1-3, the method comprising (a) contacting the nucleic acid with a primer which hybridizes to the nucleic acid in a 3 'sequence of the nucleotide variation, and (b) extending the primer to generate an amplification product comprising the nucleotide variation. In one embodiment, the nucleotide variation is a nucleotide change selected from Figures 1

3. En otra realización, la variación de nucleótido es una mutación somática. En otra realización, la variación de nucleótido es un polimorfismo en la línea germinal. 3. In another embodiment, the nucleotide variation is a somatic mutation. In another embodiment, the nucleotide variation is a germline polymorphism.

[0011] En otra realización, se proporciona un método de determinación del genotipo de una muestra biológica de un mamífero, comprendiendo el método detectar la ausencia o presencia de una variación de nucleótido en una posición de nucleótido seleccionada de las figuras 1-3 en material de ácido nucleico derivado de la muestra biológica. En una realización, la variación de nucleótido es un cambio de nucleótido seleccionado de las figuras 1-3. En otra realización, la muestra biológica es sospechosa de comprender células tumorales. En otra realización, la muestra biológica es un tumor. En una de dichas realizaciones, el tumor es un tumor de pulmón. En una de dichas realizaciones, el tumor de pulmón es un carcinoma de pulmón de célula no pequeña. En otra realización, la detección comprende llevar a cabo un proceso seleccionado entre un ensayo de extensión con cebador; un ensayo de extensión con un cebador específico de alelo; un ensayo de incorporación de nucleótido específico de alelo; un ensayo de hibridación de oligonucleótido específico de alelo; un ensayo de 5’ nucleasa; un ensayo que utiliza sondas fluorescentes; y un ensayo de unión a oligonucleótido. En otra realización, la variación de nucleótido es una mutación somática. En otra realización, la variación de nucleótido es un polimorfismo en la línea germinal. [0011] In another embodiment, a method of determining the genotype of a biological sample of a mammal is provided, the method comprising detecting the absence or presence of a nucleotide variation at a selected nucleotide position of Figures 1-3 in material. of nucleic acid derived from the biological sample. In one embodiment, the nucleotide variation is a nucleotide change selected from Figures 1-3. In another embodiment, the biological sample is suspected of comprising tumor cells. In another embodiment, the biological sample is a tumor. In one of said embodiments, the tumor is a lung tumor. In one such embodiment, the lung tumor is a non-small cell lung carcinoma. In another embodiment, the detection comprises carrying out a process selected from a primer extension assay; an extension assay with an allele specific primer; an allele specific nucleotide incorporation assay; an allele specific oligonucleotide hybridization assay; a 5 ’nuclease assay; an assay that uses fluorescent probes; and an oligonucleotide binding assay. In another embodiment, the nucleotide variation is a somatic mutation. In another embodiment, the nucleotide variation is a germline polymorphism.

[0012] En otro aspecto, se proporciona un método de clasificación de un tumor en un mamífero, comprendiendo el método detectar la presencia de una variación en un PRO o polinucleótido de PRO en una muestra biológica derivada del mamífero, en el que la muestra biológica es conocida o sospechosa de comprender células tumorales. En una realización, las células tumorales son células tumorales de pulmón. En una de dichas realizaciones, las células tumorales de pulmón son células de carcinoma de pulmón de célula no pequeña. En otra realización, la variación es una variación de nucleótido. En una de dichas realizaciones, la variación de nucleótido es en una posición de nucleótido seleccionada de las figuras 1-3. En otra de dichas realizaciones, la variación de nucleótido es un cambio de nucleótido seleccionado de las figuras 1-3. En otra de dichas realizaciones, la detección comprende llevar a cabo un proceso seleccionado entre un ensayo de extensión con cebador; un ensayo de extensión con un cebador específico de alelo; un ensayo de incorporación de nucleótido específico de alelo; un ensayo de hibridación de oligonucleótido específico de alelo; un ensayo de 5’ nucleasa; un ensayo que utiliza sondas fluorescentes; y un ensayo de unión a oligonucleótido. En otra de dichas realizaciones, la variación de nucleótido es una mutación somática. En otra de dichas realizaciones, la variación de nucleótido es un polimorfismo en la línea germinal. En otra realización, la variación es una variación de aminoácido. En una de dichas realizaciones, la variación de aminoácido es un dominio funcional de PRO seleccionado de la figura 1 ó 3. En otra de dichas realizaciones, la variación de aminoácido es en una posición de aminoácido seleccionada de la figura 1 ó 3. En otra de dichas realizaciones, la variación de aminoácido es un cambio de aminoácido seleccionado de la figura 1 ó 3. En otra realización, la variación es una variación de aminoácido en FBXW7. En una de dichas realizaciones, la variación de aminoácido en FBXW7 es en el dominio WD40. En una de dichas realizaciones, la variación de aminoácido es en una posición de aminoácido seleccionada entre G343, R399, y Y429. En otra realización, la variación es una variación de nucleótido en un polinucleótido FBXW7. En una de dichas realizaciones, la variación de nucleótido es en una región de un polinucleótido FBXW7 que codifica el dominio WD40. En otra de dichas realizaciones, la variación de nucleótido es en una posición de nucleótido seleccionada entre C153607116, C153604971, y T153604881 del cromosoma 4. En una de dichas realizaciones, la variación de nucleótido es un cambio de nucleótido seleccionado entre C153607116T, C153604971T, y T153604R81A. [0012] In another aspect, a method of classifying a tumor in a mammal is provided, the method comprising detecting the presence of a variation in a PRO or PRO polynucleotide in a biological sample derived from the mammal, in which the biological sample It is known or suspected of understanding tumor cells. In one embodiment, the tumor cells are lung tumor cells. In one such embodiment, the lung tumor cells are non-small cell lung carcinoma cells. In another embodiment, the variation is a nucleotide variation. In one of said embodiments, the nucleotide variation is in a nucleotide position selected from Figures 1-3. In another such embodiment, the nucleotide variation is a nucleotide change selected from Figures 1-3. In another of said embodiments, the detection comprises carrying out a process selected from a primer extension assay; an extension assay with an allele specific primer; an allele specific nucleotide incorporation assay; an allele specific oligonucleotide hybridization assay; a 5 ’nuclease assay; an assay that uses fluorescent probes; and an oligonucleotide binding assay. In another of said embodiments, the nucleotide variation is a somatic mutation. In another such embodiment, the nucleotide variation is a germline polymorphism. In another embodiment, the variation is an amino acid variation. In one of said embodiments, the amino acid variation is a functional PRO domain selected from Figure 1 or 3. In another such embodiment, the amino acid variation is at a selected amino acid position of Figure 1 or 3. In another of said embodiments, the amino acid variation is an amino acid change selected from Figure 1 or 3. In another embodiment, the variation is an amino acid variation in FBXW7. In one of said embodiments, the amino acid variation in FBXW7 is in the WD40 domain. In one of said embodiments, the amino acid variation is at an amino acid position selected from G343, R399, and Y429. In another embodiment, the variation is a nucleotide variation in an FBXW7 polynucleotide. In one such embodiment, the nucleotide variation is in a region of an FBXW7 polynucleotide encoding the WD40 domain. In another of said embodiments, the nucleotide variation is at a nucleotide position selected from C153607116, C153604971, and T153604881 of chromosome 4. In one such embodiment, the nucleotide variation is a nucleotide change selected from C153607116T, C153604971T, and T153604R81A.

[0013] En otro aspecto, se proporciona un método para predecir si un tumor responderá a un agente terapéutico que reconoce un PRO o un polipéptido PRO, comprendiendo el método determinar si el tumor comprende una variación en un PRO o polinucleótido PRO, en el que la presencia de una variación indica que el tumor responderá al agente terapéutico. En una realización, el tumor es un tumor de pulmón. En una de dichas realizaciones, el tumor de pulmón es un carcinoma de pulmón de célula no pequeña. En otra realización, la variación es una variación de nucleótido. En una de dichas realizaciones, la variación de nucleótido es en una posición de nucleótido seleccionada de las figuras 1-3. En otra de dichas realizaciones, la variación de nucleótido es un cambio de nucleótido seleccionado de las figuras 1-3. En otra de dichas realizaciones, la variación de nucleótido es una mutación somática. En otra de dichas realizaciones, la variación de nucleótido es un polimorfismo en la línea germinal. En otra realización, la variación es una variación de aminoácido. En una de dichas realizaciones, la variación de aminoácido es en un dominio funcional de PRO seleccionado de la figura 1 ó 3. En otra de dichas realizaciones, la variación de aminoácido es en una posición de aminoácido seleccionada de la figura 1 ó 3. En otra de dichas realizaciones, la variación de aminoácido es un cambio de aminoácido seleccionado de la figura 1 ó 3. [0013] In another aspect, a method is provided to predict whether a tumor will respond to a therapeutic agent that recognizes a PRO or a PRO polypeptide, the method comprising determining whether the tumor comprises a variation in a PRO or PRO polynucleotide, in which the presence of a variation indicates that the tumor will respond to the therapeutic agent. In one embodiment, the tumor is a lung tumor. In one such embodiment, the lung tumor is a non-small cell lung carcinoma. In another embodiment, the variation is a nucleotide variation. In one of said embodiments, the nucleotide variation is in a nucleotide position selected from Figures 1-3. In another such embodiment, the nucleotide variation is a nucleotide change selected from Figures 1-3. In another of said embodiments, the nucleotide variation is a somatic mutation. In another such embodiment, the nucleotide variation is a germline polymorphism. In another embodiment, the variation is an amino acid variation. In one of said embodiments, the amino acid variation is in a functional domain of PRO selected from Figure 1 or 3. In another of said embodiments, the amino acid variation is in a selected amino acid position of Figure 1 or 3. In Another such embodiment, the amino acid variation is an amino acid change selected from Figure 1 or 3.

[0014] Éstas y otras realizaciones se describen en la siguiente descripción escrita. [0014] These and other embodiments are described in the following written description.

BREVE DESCRIPCIÓN DE LAS FIGURAS BRIEF DESCRIPTION OF THE FIGURES

[0015] La figura 1 es una tabla de variaciones de nucleótido en las regiones codificantes de genes seleccionados. También se proporcionan las variaciones de aminoácidos resultantes. Las variaciones de nucleótidos se identificaron en un ácido nucleico derivado de tumores de pulmón mediante la detección de reparación de apareamientos erróneos (MRD), tal como se describe en ejemplo A. [0015] Figure 1 is a table of nucleotide variations in the coding regions of selected genes. The resulting amino acid variations are also provided. Nucleotide variations were identified in a nucleic acid derived from lung tumors by detecting mismatch repair (MRD), as described in example A.

La figura 2 es una tabla de variaciones de nucleótidos que afectan al empalme de ARNm transcrito a partir de genes seleccionados. Las variaciones de nucleótidos se identificaron en ácido nucleico derivado de tumores de pulmón utilizando la detección de reparación de apareamientos erróneos (MRD), tal como se describe en ejemplo A. Figure 2 is a table of nucleotide variations that affect the splicing of mRNA transcribed from selected genes. Nucleotide variations were identified in lung tumor derived nucleic acid using the mismatch repair detection (MRD), as described in example A.

La figura 3 es una tabla de variaciones de nucleótidos en las regiones codificantes de genes seleccionados. También se proporcionan las variaciones de aminoácidos resultantes. Las variaciones de nucleótidos se identificaron en ácido nucleico derivado de tumores de pulmón utilizando secuenciación Sanger, tal como se describe en el ejemplo B. Figure 3 is a table of nucleotide variations in the coding regions of selected genes. The resulting amino acid variations are also provided. Nucleotide variations were identified in nucleic acid derived from lung tumors using Sanger sequencing, as described in example B.

DESCRIPCIÓN DETALLADA DE LAS REALIZACIONES DETAILED DESCRIPTION OF THE EMBODIMENTS

I. DEFINICIONES I. DEFINITIONS

[0016] Con el objetivo de interpretar esta memoria, se aplicarán las siguientes definiciones y cuando sea apropiado, los términos utilizados en singular también incluirán el plural y viceversa. En el caso de que cualquiera de las definiciones indicadas a continuación entre en conflicto con cualquier documento incorporado aquí por referencia, la definición mostrada a continuación tendrá preferencia. [0016] In order to interpret this report, the following definitions will apply and when appropriate, the terms used in the singular will also include the plural and vice versa. In the event that any of the definitions indicated below conflict with any document incorporated herein by reference, the definition shown below shall have preference.

[0017] El término "polinucleótido” o “ácido nucleico”, utilizados indistintamente aquí, se refiere a polímeros de nucleótidos de cualquier longitud e incluyen ADN y ARN. Los nucleótidos pueden ser desoxirribonucleótidos, ribonucleótidos, nucleótidos modificados o bases y/o sus análogos, o cualquier sustrato que se puede incorporar en un polímero mediante ADN o ARN polimerasa. Un polinucleótido puede comprender nucleótidos modificados, tales como nucleótidos metilados y sus análogos. Si está presente, la modificación en la estructura de nucleótidos se puede realizar antes o después del ensamblaje del polímero. La secuencia de nucleótidos se puede interrumpir mediante componentes no nucleotídicos. Un polinucleótido se puede modificar adicionalmente después de la polimerización, tal como mediante la conjugación con un componente marcador. Otros tipos de modificaciones incluyen, por ejemplo, “bloqueadores”, sustitución de uno o más nucleótidos naturales con un análogo, modificaciones internucleótidos, tales como, por ejemplo, aquellas con uniones no cargadas (por ejemplo, metil fosfonatos, fosfotriésteres, fosfoamidatos, carbamatos, etc.) y con uniones cargadas (por ejemplo, fosforotioatos, fosforoditioatos, etc.), aquellas que contienen grupos colgando, tales como, por ejemplo, proteínas (por ejemplo, nucleasas, toxinas, anticuerpos, péptidos señal, poli-L-lisina, etc.), aquellas con intercaladores (por ejemplo, acridina, psoralen, etc.), aquellas que contienen quelantes (por ejemplo, metales, metales radioactivos, boro, metales oxidantes, etc.), aquellas que contienen alquilantes, aquellas con uniones modificadas (por ejemplo, ácidos nucleicos alfa anoméricos, etc.), así como formas no modificadas del polinucleótido o polinucleótidos. Además, se puede sustituir cualquier grupo hidroxilo presente normalmente en los azúcares, por ejemplo, por grupos fosfonato, grupos fosfato, protegidos por grupos protectores estándar o activados para preparar uniones adicionales a nucleótidos adicionales, o se pueden conjugar a soportes sólidos. El OH 5’ y 3’ terminal se puede fosforilar o sustituir con aminas o restos de grupos de bloqueo orgánicos de 1 a 20 átomos de carbono. También se pueden derivar otros hidroxilos a grupos protectores estándar. Los polinucleótidos también pueden contener formas análogas de azúcares de ribosa o desoxirribosa que son conocidas generalmente en la técnica, incluyendo, por ejemplo, 2’-Ometil-2’-O-alil-, 2’-fluoro o 2’-azido-ribosa, análogos de azúcares carbocíclicos, azúcares alfa-anoméricos, azúcares epiméricos, tales como arabinosa, xilosas o lixosas, azúcares de piranosa, azúcares de furanosa, sedoheptulosas, análogos acíclicos y análogos de nucleósidos básicos, tales como metil ribósido. Se pueden sustituir uno o más enlaces fosfodiéster por grupos de unión alternativos. Estos grupos de unión alternativos incluyen, pero sin limitación, realizaciones en las que el fosfato se sustituye por P(O)S ("tioato"), P(S)S ("ditioato"), "(O)NR2 ("amidato"), P(O)R, P(O)OR’, CO o CH2 ("formacetal"), en que cada R o R’ es independientemente H o alquilo sustituido o no sustituido (1-20 C) que opcionalmente contienen una unión éter (-O-), arilo, alquenilo, cicloalquilo, cicloalquenilo o araldilo. No todas las uniones en un polinucleótido necesitan ser idénticas. La descripción anterior se aplica a todos los polinucleótidos referidos aquí, incluyendo ARN y ADN. [0017] The term "polynucleotide" or "nucleic acid", used interchangeably herein, refers to nucleotide polymers of any length and includes DNA and RNA. The nucleotides can be deoxyribonucleotides, ribonucleotides, modified nucleotides or bases and / or their analogs, or any substrate that can be incorporated into a polymer by DNA or RNA polymerase. A polynucleotide may comprise modified nucleotides, such as methylated nucleotides and their analogs. If present, modification in the nucleotide structure can be performed before or after polymer assembly. The nucleotide sequence can be interrupted by non-nucleotide components. A polynucleotide can be further modified after polymerization, such as by conjugation with a marker component. Other types of modifications include, for example, "blockers", substitution of one or more natural nucleotides with an analog, internucleotide modifications, such as, for example, those with uncharged junctions (eg, methyl phosphonates, phosphotriesters, phosphoamidates, carbamates , etc.) and with charged junctions (for example, phosphorothioates, phosphorodithioates, etc.), those containing hanging groups, such as, for example, proteins (for example, nucleases, toxins, antibodies, signal peptides, poly-L- lysine, etc.), those with interleavers (for example, acridine, psoralen, etc.), those containing chelants (for example, metals, radioactive metals, boron, oxidizing metals, etc.), those containing alkylating agents, those with modified junctions (eg, anomeric alpha nucleic acids, etc.), as well as unmodified forms of the polynucleotide or polynucleotides. In addition, any hydroxyl group normally present in sugars can be substituted, for example, by phosphonate groups, phosphate groups, protected by standard protecting groups or activated to prepare additional bonds to additional nucleotides, or they can be conjugated to solid supports. The 5 ’and 3’ terminal OH can be phosphorylated or substituted with amines or organic block groups of 1 to 20 carbon atoms. Other hydroxyls can also be derived to standard protecting groups. The polynucleotides may also contain analogous forms of ribose or deoxyribose sugars that are generally known in the art, including, for example, 2'-Omethyl-2'-O-allyl, 2'-fluoro or 2'-azido-ribose , analogs of carbocyclic sugars, alpha-anomeric sugars, epimeric sugars, such as arabinose, xylose or lixose, pyranose sugars, furane sugars, sedoheptuloses, acyclic analogs and basic nucleoside analogs, such as methyl riboside. One or more phosphodiester bonds can be substituted by alternative binding groups. These alternative binding groups include, but are not limited to, embodiments in which the phosphate is replaced by P (O) S (" thioate "), P (S) S (" dithioate "), " (O) NR2 (" amidate "), P (O) R, P (O) OR ', CO or CH2 (" formacetal "), in which each R or R' is independently H or substituted or unsubstituted alkyl (1-20 C) which optionally contain an ether (-O-), aryl, alkenyl, cycloalkyl, cycloalkenyl or araldyl linkage. Not all junctions in a polynucleotide need to be identical. The above description applies to all polynucleotides referred to herein, including RNA and DNA.

[0018] “Oligonucleótido," tal como se utiliza aquí, se refiere a polinucleótidos cortos de una cadena que tienen por lo menos aproximadamente siete nucleótidos de longitud y menos de aproximadamente 250 nucleótidos de longitud. Los oligonucleótidos pueden ser sintéticos. Los términos “oligonucleótido” y “polinucleótido” no se excluyen mutuamente. La descripción anterior para polinucleótidos es igualmente y totalmente aplicable a oligonucleótidos. [0018] "Oligonucleotide, " As used herein, it refers to short chain polynucleotides that are at least about seven nucleotides in length and less than about 250 nucleotides in length. The oligonucleotides can be synthetic. The terms "oligonucleotide" and "polynucleotide" are not mutually exclusive. The above description for polynucleotides is equally and fully applicable to oligonucleotides.

[0019] El término “cebador” se refiere a un polinucleótido de cadena única que es capaz de hibridarse a un ácido nucleico y que permite la polimerización de un ácido nucleico complementario, generalmente proporcionando un grupo 3’-OH libre. [0019] The term "primer" refers to a single chain polynucleotide that is capable of hybridizing to a nucleic acid and that allows the polymerization of a complementary nucleic acid, generally providing a free 3'-OH group.

[0020] El término “PRO” se refiere a una proteína codificada por cualquiera de los genes indicados en las figuras 13, incluyendo formas de tipo salvaje y variantes de la misma. Dichas formas incluyen “longitud completa”, formas no procesadas de PRO; formas de PRO que resultan del procesamiento celular; variantes de PRO naturales, por ejemplo, PRO resultante de empalme alternativo, variaciones alélicas o mutación espontánea; y fragmentos o variantes de una PRO nativa que mantienen por lo menos una actividad biológica de PRO, a menos que se indique lo contrario. [0020] The term "PRO" refers to a protein encoded by any of the genes indicated in Figures 13, including wild-type forms and variants thereof. Such forms include "full length", unprocessed forms of PRO; PRO forms that result from cellular processing; natural PRO variants, for example, PRO resulting from alternative splicing, allelic variations or spontaneous mutation; and fragments or variants of a native PRO that maintain at least one biological activity of PRO, unless otherwise indicated.

[0021] El término "polinucleótido de PRO" o "ácido nucleico que codifica PRO" se refiere a un gen o secuencia codificante (por ejemplo, un ARNm o secuencia codificante de ADNc) que codifica un PRO, a menos que se indique lo contrario. [0021] The term "PRO polynucleotide" or "nucleic acid encoding PRO" refers to a gene or coding sequence (eg, an mRNA or cDNA coding sequence) that encodes a PRO, unless otherwise indicated.

[0022] El término "variación de nucleótido" se refiere a un cambio en la secuencia de nucleótidos (por ejemplo, una inserción, deleción, inversión o sustitución de uno o más nucleótidos, tales como un polimorfismo de nucleótido único (SNP)) en relación a una secuencia de referencia (por ejemplo, una secuencia de tipo salvaje). El término también comprende el correspondiente cambio en el complemento de la secuencia de nucleótidos, a menos que se indique lo contrario. Una variación de nucleótido puede ser una mutación somática o un polimorfismo en la línea germinal [0022] The term " nucleotide variation " refers to a change in the nucleotide sequence (for example, an insertion, deletion, inversion or substitution of one or more nucleotides, such as a single nucleotide polymorphism (SNP)) in relation to a reference sequence (e.g., a wild type sequence). The term also includes the corresponding change in complement of the nucleotide sequence, unless otherwise indicated. A nucleotide variation can be a somatic mutation or a germline polymorphism

[0023] El término "variación de aminoácido" se refiere a un cambio en una secuencia de aminoácidos (por ejemplo, una inserción, sustitución o deleción de uno o más aminoácidos, tales como una deleción interna o un truncamiento N o C-terminal) en relación con una secuencia de referencia. [0023] The term " amino acid variation " refers to a change in an amino acid sequence (for example, an insertion, substitution or deletion of one or more amino acids, such as an internal deletion or an N or C-terminal truncation) in relation to a reference sequence.

[0024] El término "variación" se refiere a una variación de nucleótido o una variación de aminoácido. [0024] The term "variation" It refers to a nucleotide variation or an amino acid variation.

[0025] El término "una variación de nucleótido en una posición de nucleótido seleccionada de la figura (a) ###" y variantes gramaticales del mismo (donde la "Figura(s) ###" se refiere a cualquiera de las figuras 1-3) se refieren a una variación de nucleótidos en una secuencia de polinucleótido de PRO en cualquiera de las posiciones de nucleótidos indicados en la columna 5 de cualquiera de las figuras 1-3, incluyendo, pero sin limitación, los cambios de nucleótidos específicos indicados en la columna 5 de cualquiera de las figuras 1-3. Por ejemplo y con fines ilustrativos, con referencia a la columna 5 en la primera fila de la figura 1, una variación de nucleótidos en la posición de nucleótido 130790136 de un polinucleótido ABL comprende cualquier cambio en esa posición de nucleótido, incluyendo, pero sin limitación, el cambio de nucleótido específico, es decir la sustitución G/T, indicada en la columna 5. El término también comprende el correspondiente cambio en el complemento de la secuencia de nucleótidos, a menos que se indique lo contrario. [0025] The term "a variation of nucleotide at a selected nucleotide position of Figure (a) ###" and grammatical variants thereof (where "Figure (s) ###" refers to any of Figures 1-3) refer to a variation of nucleotides in a PRO polynucleotide sequence at any of the positions of nucleotides indicated in column 5 of any of Figures 1-3, including, but not limited to, the specific nucleotide changes indicated in column 5 of any of Figures 1-3. For example and for illustrative purposes, with reference to column 5 in the first row of Figure 1, a variation of nucleotides at nucleotide position 130790136 of an ABL polynucleotide comprises any change in that nucleotide position, including, but not limited to , the specific nucleotide change, ie the G / T substitution, indicated in column 5. The term also includes the corresponding change in the complement of the nucleotide sequence, unless otherwise indicated.

[0026] El término "un cambio de nucleótido de seleccionado de la figura(s) ###" y variantes gramaticales del mismo (donde "figura(s) ###" se refiere a cualquiera de las figuras 1-3) se refieren a cualquiera de los cambios de nucleótidos específicos indicados en la columna 5 de cualquiera de las figuras 1-3. Con fines ilustrativos, un ejemplo de un cambio de nucleótido seleccionado de la figura 1 es la sustitución G/T en la posición de nucleótido 130790136 de un polinucleótido ABL, tal como se muestra en la columna 5 en la primera fila de la figura 1. [0026] The term " a nucleotide change of selected from figure (s) ### " and grammatical variants thereof (where "figure (s) ###" refers to any of Figures 1-3) refer to any of the specific nucleotide changes indicated in column 5 of any of Figures 1 -3. For illustrative purposes, an example of a selected nucleotide change of Figure 1 is the G / T substitution at nucleotide position 130790136 of an ABL polynucleotide, as shown in column 5 in the first row of Figure 1.

[0027] El término "una variación de aminoácido en una posición de aminoácido seleccionada entre la figura(s) ###" y variantes gramaticales del mismo (donde "figura(s) ###" se refiere a cualquiera de las figuras 1-3) se refieren a una variación de aminoácidos en la secuencia de aminoácidos de PRO en cualquiera de las posiciones de aminoácidos indicadas en la columna 6 de la figura 1 ó 3, incluyendo, pero sin limitación, los cambios de aminoácidos específicos indicados en la columna 6 de la figura 1 ó 3. Por ejemplo y con fines ilustrativos, en referencia a la columna 6 en la primera fila de la figura 1, una variación de aminoácidos en la posición de aminoácido 969 de ABL comprende cualquier cambio en esa posición de aminoácido, incluyendo, pero sin limitación, el cambio de aminoácido específico, es decir, la sustitución A>S, indicada en la columna 6. [0027] The term "an amino acid variation at an amino acid position selected from the figure (s) ###" and grammatical variants thereof (where "figure (s) ###" refers to any of Figures 1-3) refer to a variation of amino acids in the amino acid sequence of PRO at any of the amino acid positions indicated in column 6 of Figure 1 or 3, including, but not limited to, the specific amino acid changes indicated in column 6 of Figure 1 or 3. For example and for illustrative purposes, referring to column 6 in the First row of Figure 1, a variation of amino acids at amino acid position 969 of ABL comprises any change in that amino acid position, including, but not limited to, the specific amino acid change, that is, the A> S substitution indicated in column 6.

[0028] El término "un cambio de aminoácido seleccionado de la Figura(s) ###" y variantes gramaticales del mismo (donde "figura(s) ###" se refiere a cualquiera de las figuras 1-3) se refieren a cualquiera de los cambios de aminoácidos específicos indicados en la columna 6 de la figura 1 ó 3. Con fines ilustrativos, un ejemplo de un cambio de aminoácido seleccionado de la figura 1 es la sustitución A>S en la posición de aminoácido 969 de ABL, tal como se muestra en la columna 6 en la primera fila de la figura 1. [0028] The term "an amino acid change selected from Figure (s) ###" and grammatical variants thereof (where "figure (s) ###" refers to any of Figures 1-3) refer to any of the specific amino acid changes indicated in column 6 of Figure 1 or 3 For illustrative purposes, an example of a selected amino acid change of Figure 1 is the A> S substitution at amino acid position 969 of ABL, as shown in column 6 in the first row of Figure 1.

[0029] El término "dominio funcional de PRO" se refiere a cualquiera de los dominios de proteína indicados en cualquiera de las figuras 1-3. [0029] The term "PRO functional domain" refers to any of the protein domains indicated in any of Figures 1-3.

[0030] El término "variación activante" se refiere a una variación en un gen o secuencia codificante que da lugar a una forma más activa del polipéptido codificado, en relación con el polipéptido de tipo salvaje. [0030] The term " activating variation " refers to a variation in a gene or coding sequence that results in a more active form of the encoded polypeptide, relative to the wild type polypeptide.

[0031] El término "array" o "microarray" se refiere a una disposición ordenada de elementos de “array” hibridables, preferiblemente sondas de polinucleótidos (por ejemplo, oligonucleótidos), en un sustrato. El sustrato puede ser un sustrato sólido, tal como un portaobjetos de vidrio, o un sustrato semisólido, tal como una membrana de nitrocelulosa. [0031] The term " array " or "microarray" refers to an ordered arrangement of hybridizable "array" elements, preferably polynucleotide probes (eg, oligonucleotides), in a substrate. The substrate can be a solid substrate, such as a glass slide, or a semi-solid substrate, such as a nitrocellulose membrane.

[0032] El término "amplificación" se refiere al proceso de producir una o más copias de una secuencia de ácido nucleico de referencia o su complemento. La amplificación puede ser lineal o exponencial (por ejemplo, PCR). Una “copia” no significa necesariamente una complementariedad o identidad de secuencia perfecta en relación con la secuencia de molde. Por ejemplo, las copias pueden incluir análogos de nucleótidos, tales como desoxinosina, alteraciones intencionales en la secuencia (tales como alteraciones en la secuencia introducidos a través de un cebador que comprende una secuencia que es hibridable, pero no totalmente complementaria, con el molde) y/o errores en la secuencia que ocurren durante la amplificación. [0032] The term " amplification " refers to the process of producing one or more copies of a reference nucleic acid sequence or its complement. The amplification can be linear or exponential (for example, PCR). A "copy" does not necessarily mean a perfect sequence complementarity or identity in relation to the template sequence. For example, copies may include nucleotide analogs, such as deoxinosine, intentional sequence alterations (such as sequence alterations introduced through a primer comprising a sequence that is hybridizable, but not fully complementary, with the template) and / or sequence errors that occur during amplification.

[0033] El término "oligonucleótido específico de alelo" se refiere a un oligonucleótido que se hibrida a una región de un ácido nucleico diana que comprende una variación de nucleótido (generalmente una sustitución). "Hibridación específica de alelo" significa que, cuando un oligonucleótido específico de alelo se hibrida a su ácido nucleico diana, un nucleótido en el oligonucleótido específico de alelo se empareja específicamente en las bases con la variación de nucleótido. Un oligonucleótido específico de alelo capaz de la hibridación específica de alelo con respecto a una variación de nucleótido particular se dice que es “específico” para esa variación. [0033] The term "allele specific oligonucleotide" refers to an oligonucleotide that hybridizes to a region of a target nucleic acid comprising a nucleotide variation (generally a substitution). " Allele specific hybridization " means that, when an allele-specific oligonucleotide hybridizes to its target nucleic acid, a nucleotide in the allele-specific oligonucleotide is specifically matched at the bases with the nucleotide variation. An allele specific oligonucleotide capable of allele specific hybridization with respect to a particular nucleotide variation is said to be "specific" for that variation.

[0034] El término "cebador específico de alelo" se refiere a un oligonucleótido específico de alelo que es un cebador. [0034] The term "allele specific primer" refers to an allele specific oligonucleotide that is a primer.

[0035] El término "ensayo de extensión con cebador” se refiere a un ensayo en el que se añaden nucleótidos a un ácido nucleico, dando lugar a un ácido nucleico más largo, o “producto de extensión” que se detecta directa o indirectamente. [0035] The term "primer extension assay" refers to an assay in which nucleotides are added to a nucleic acid, resulting in a longer nucleic acid, or "extension product" that is detected directly or indirectly. .

[0036] El término "ensayo de incorporación de nucleótido específico de alelo" se refiere a un ensayo de extensión con cebador en el que un cebador se (a) hibrida a un ácido nucleico diana en una región que es 3’ de una variación de nucleótido y (b) extiende por una polimerasa, incorporando así en el producto de extensión un nucleótido que es complementario a la variación de nucleótido. [0036] The term "allele-specific nucleotide incorporation assay" refers to a primer extension assay in which a primer hybridizes (a) to a target nucleic acid in a region that is 3 'of a nucleotide variation and (b) extends through a polymerase, thus incorporating into the product of extension a nucleotide that is complementary to the variation of nucleotide.

[0037] El término "ensayo de extensión con cebador específico de alelo" se refiere a un ensayo de extensión con cebador en el que el cebador específico de alelo se hibrida a un ácido nucleico diana y se extiende. [0037] The term "extension assay with allele specific primer" refers to a primer extension assay in which the allele specific primer hybridizes to a target nucleic acid and extends.

[0038] El término "ensayo de hibridación de oligonucleótido específico de alelo" se refiere a un ensayo en el que (a) un oligonucleótido específico de alelo se hibrida a un ácido nucleico diana y (b) la hibridación se detecta directa o indirectamente. [0038] The term "allele-specific oligonucleotide hybridization assay" refers to an assay in which (a) an allele-specific oligonucleotide hybridizes to a target nucleic acid and (b) hybridization is detected directly or indirectly.

[0039] El término "ensayo de 5 nucleasa" se refiere a un ensayo en el que la hibridación de un oligonucleótido específico de alelo a un ácido nucleico diana permite la división nucleolítica de la sonda hibridada, dando lugar a una señal detectable. [0039] The term "5 nuclease assay" refers to an assay in which the hybridization of an allele-specific oligonucleotide to a target nucleic acid allows the nucleolytic division of the hybridized probe, giving rise to a detectable signal.

[0040] El término "ensayo que utiliza sondas fluorescentes" se refiere a un ensayo en el que la hibridación de un oligonucleótido específico de alelo a un ácido nucleico diana da lugar a un nivel de señal detectable que es superior al nivel de señal detectable emitido por el oligonucleótido libre. [0040] The term "assay using fluorescent probes" refers to an assay in which hybridization of an allele-specific oligonucleotide to a target nucleic acid results in a detectable signal level that is greater than the level of the detectable signal emitted by the free oligonucleotide.

[0041] El término "ensayo de unión a oligonucleótido" se refiere a un ensayo en el que un oligonucleótido específico de alelo y un segundo oligonucleótido se hibridan adyacentes entre sí en un ácido nucleico diana y se unen juntos (ya sea directa o indirectamente a través de nucleótidos que intervienen), y el producto de unión se detecta directa o indirectamente. [0041] The term "oligonucleotide binding assay" refers to an assay in which an allele specific oligonucleotide and a second oligonucleotide hybridize adjacent to each other in a target nucleic acid and bind together (either directly or indirectly through intervening nucleotides), and the binding product It is detected directly or indirectly.

[0042] El término "secuencia diana," "ácido nucleico diana," o "secuencia de ácido nucleico diana" se refiere en general a una secuencia de polinucleótido de interés en la que reside una variación de nucleótido es sospechosa o conocida, incluyendo copias de dicho ácido nucleico diana generado por amplificación. [0042] The term " target sequence, " " target nucleic acid, " or "target nucleic acid sequence" it generally refers to a polynucleotide sequence of interest in which a variation of nucleotide is suspected or known, including copies of said target nucleic acid generated by amplification.

[0043] El término "detección" incluye cualquier medio de detección, incluyendo la detección directa e indirecta. [0043] The term "detection" includes any means of detection, including direct and indirect detection.

[0044] El término "diagnóstico" se utiliza aquí para referirse a la identificación o clasificación de un estado, enfermedad o condición molecular o patológica. Por ejemplo, “diagnóstico” se puede referir a la identificación de un tipo particular de cáncer, por ejemplo un cáncer de pulmón. “Diagnóstico” también se puede referir a la clasificación de un tipo particular de cáncer, por ejemplo, mediante histología (por ejemplo, un carcinoma de pulmón de célula no pequeña), mediante características moleculares (por ejemplo, un cáncer de pulmón caracterizado por una variación [0044] The term "diagnosis" It is used here to refer to the identification or classification of a molecular or pathological state, disease or condition. For example, "diagnosis" may refer to the identification of a particular type of cancer, for example a lung cancer. "Diagnosis" can also refer to the classification of a particular type of cancer, for example, by histology (for example, a non-small cell lung carcinoma), by molecular characteristics (for example, a lung cancer characterized by a variation

o variaciones de nucleótidos o aminoácidos en un gen o proteína particular), o ambas. or variations of nucleotides or amino acids in a particular gene or protein), or both.

[0045] El término "pronóstico" se utiliza aquí para referirse a la predicción de la probabilidad de muerte o progresión atribuible a cáncer, incluyendo, por ejemplo, reaparición, extensión metastásica, y resistencia a fármacos, de una enfermedad neoplásica, tal como cáncer. [0045] The term "forecast" It is used here to refer to the prediction of the probability of death or progression attributable to cancer, including, for example, recurrence, metastatic extension, and drug resistance, of a neoplastic disease, such as cancer.

[0046] El término "predicción" se utiliza aquí para referirse a la probabilidad de que un paciente responda favorable o desfavorablemente a un fármaco o grupo de fármacos. En una realización, la predicción de refiere al grado de dichas respuestas. En otra realización, la predicción se refiere a si es posible y/o la probabilidad de que un paciente sobreviva siguiendo el tratamiento, por ejemplo, el tratamiento con un agente terapéutico particular y/o eliminación quirúrgica del tumor primario, y/o quimioterapia durante un cierto periodo de tiempo sin reaparición del cáncer. Los métodos predictivos de la invención se pueden utilizar clínicamente para tomar decisiones sobre el tratamiento mediante la elección de las modalidades de tratamiento más apropiadas para cualquier paciente particular. Los métodos predictivos de la presente invención son herramientas valiosas en la predicción de si un paciente es probable que responda de manera favorable a una pauta de tratamiento, tal como una pauta de tratamiento terapéutico, incluyendo, por ejemplo, la administración de un agente terapéutico determinado o una combinación, intervención quirúrgica, quimioterapia, etc., o si es probable la supervivencia a largo plazo del paciente siguiendo la pauta terapéutica. [0046] The term "prediction" It is used here to refer to the probability that a patient responds favorably or unfavorably to a drug or group of drugs. In one embodiment, the prediction refers to the degree of said responses. In another embodiment, the prediction refers to whether it is possible and / or the likelihood that a patient will survive following treatment, for example, treatment with a particular therapeutic agent and / or surgical removal of the primary tumor, and / or chemotherapy during a certain period of time without recurrence of cancer. The predictive methods of the invention can be used clinically to make treatment decisions by choosing the most appropriate treatment modalities for any particular patient. The predictive methods of the present invention are valuable tools in predicting whether a patient is likely to respond favorably to a treatment regimen, such as a therapeutic treatment regimen, including, for example, the administration of a particular therapeutic agent. or a combination, surgical intervention, chemotherapy, etc., or if the long-term survival of the patient is likely following the therapeutic guideline.

[0047] Los términos “trastorno proliferativo celular” y “trastorno proliferativo” se refieren a trastornos que están asociados con un grado medible de proliferación celular anormal. En una realización, el trastorno proliferativo celular es cáncer. [0047] The terms "cell proliferative disorder" and "proliferative disorder" refer to disorders that are associated with a measurable degree of abnormal cell proliferation. In one embodiment, the cell proliferative disorder is cancer.

[0048] "Tumor", tal como se utiliza aquí, se refiere al crecimiento y proliferación de todas las células neoplásicas, tanto malignas como benignas, y a todas las células y tejidos precancerosos y cancerosos. Los términos “cáncer”, “canceroso”, “trastorno proliferativo celular” y “tumor” no se excluyen mutuamente tal como se refieren aquí. [0048] "Tumor", as used herein, refers to the growth and proliferation of all neoplastic cells, both malignant and benign, and all precancerous and cancerous cells and tissues. The terms "cancer", "cancerous", "cell proliferative disorder" and "tumor" are not mutually exclusive as referred to herein.

[0049] Los términos “cáncer” y “canceroso” se refieren o describen la condición fisiológica en mamíferos que se caracteriza habitualmente por un crecimiento y proliferación celular no regulada. Entre los ejemplos de cáncer se incluyen, pero sin limitación, carcinoma, linfoma (por ejemplo, linfoma de Hodgkin y no de Hodking), blastoma, sarcoma, y leucemia. Ejemplos más particulares de dichos cánceres incluyen, cáncer de célula escamosa, cáncer de pulmón de célula pequeña, cáncer de pulmón de célula no pequeña, adenocarcinoma del pulmón, carcinoma escamoso del pulmón, cáncer del peritoneo, cáncer hepatocelular, cáncer de células renales, cáncer gastrointestinal, cáncer gástrico, cáncer de esófago, cáncer pancreático, glioma, cáncer cervical, cáncer de ovario, cáncer de hígado, cáncer de vejiga, hematoma, cáncer de mama, cáncer de colon, cáncer rectal, cáncer de pulmón, carcinoma de endometrio o uterino, carcinoma de glándula salivar, cáncer de riñón, cáncer de hígado, cáncer de próstata, cáncer de vulva, cáncer de tiroides, carcinoma hepático, melanoma, leucemia y otros trastornos linfoproliferativos, y varios tipos de cáncer de cabeza y cuello. [0049] The terms "cancer" and "cancerous" refer to or describe the physiological condition in mammals that is usually characterized by unregulated cell growth and proliferation. Examples of cancer include, but are not limited to, carcinoma, lymphoma (for example, Hodgkin lymphoma and non-Hodking lymphoma), blastoma, sarcoma, and leukemia. More particular examples of such cancers include, squamous cell cancer, small cell lung cancer, non-small cell lung cancer, lung adenocarcinoma, squamous lung carcinoma, peritoneum cancer, hepatocellular cancer, renal cell cancer, cancer gastrointestinal, gastric cancer, esophageal cancer, pancreatic cancer, glioma, cervical cancer, ovarian cancer, liver cancer, bladder cancer, hematoma, breast cancer, colon cancer, rectal cancer, lung cancer, endometrial carcinoma or uterine, salivary gland carcinoma, kidney cancer, liver cancer, prostate cancer, vulvar cancer, thyroid cancer, liver carcinoma, melanoma, leukemia and other lymphoproliferative disorders, and various types of head and neck cancer.

[0050] El término "tumor de pulmón" se refiere a cualquier tumor del pulmón, incluyendo, pero sin limitación, carcinoma de pulmón de célula pequeña y carcinoma de pulmón de célula no pequeña, el segundo, incluyendo, pero sin limitación, adenocarcinoma, carcinoma escamoso y carcinoma de célula grande. [0050] The term " lung tumor " refers to any lung tumor, including, but not limited to, small cell lung carcinoma and non-small cell lung carcinoma, the second, including, but not limited to, adenocarcinoma, squamous carcinoma and large cell carcinoma.

[0051] El término "neoplasma" o "célula neoplásica" se refiere a un tejido o célula anormal que prolifera más rápidamente que los correspondientes tejidos o células normales y continúa creciendo después de la eliminación del estímulo que inició el crecimiento. [0051] The term " neoplasma " or "neoplastic cell" It refers to an abnormal tissue or cell that proliferates more rapidly than the corresponding normal tissues or cells and continues to grow after the removal of the stimulus that initiated the growth.

[0052] Una "célula de tumor de pulmón" se refiere a una célula de tumor de pulmón, ya sea in vivo o in vitro, y comprende líneas celulares derivadas de células tumorales de pulmón. [0052] A "lung tumor cell" It refers to a lung tumor cell, either in vivo or in vitro, and comprises cell lines derived from lung tumor cells.

[0053] Tal como se utiliza aquí, “tratamiento” (y variaciones, tales como “tratar” o “que trata”) se refiere a la intervención clínica en un intento por alterar la evolución natural del individuo o célula en tratamiento, y se puede realizar para profilaxis o durante la evolución de la patología clínica. Los efectos deseables del tratamiento incluyen la prevención de la aparición o reaparición de la enfermedad, el alivio de síntomas, la disminución de cualquier consecuencia patológica directa o indirecta de la enfermedad, prevención de la metástasis, disminución de la velocidad de progresión de la enfermedad, mejora o paliación del estado patológico y la remisión o pronóstico mejorado. [0053] As used herein, "treatment" (and variations, such as "treating" or "treating") refers to clinical intervention in an attempt to alter the natural evolution of the individual or cell under treatment, and Can perform for prophylaxis or during the evolution of clinical pathology. Desirable effects of the treatment include the prevention of the onset or recurrence of the disease, the relief of symptoms, the decrease of any direct or indirect pathological consequences of the disease, prevention of metastasis, decrease in the rate of disease progression, improvement or palliation of the pathological state and improved remission or prognosis.

[0054] Un “individuo" es un vertebrado. En ciertas realizaciones, el vertebrado es un mamífero. Entre los mamíferos se incluyen, pero sin limitaciones, animales de granja (tales como vacas), animales de competición, mascotas (como gatos, perros o caballos), primates (incluyendo primates humano y no humano) y roedores (por ejemplo, ratones y ratas). En ciertas realizaciones, el mamífero es un humano. [0054] An "individual" It is a vertebrate. In certain embodiments, the vertebrate is a mammal. Mammals include, but are not limited to, farm animals (such as cows), competition animals, pets (such as cats, dogs or horses), primates (including human and non-human primates) and rodents (eg, mice and rats) In certain embodiments, the mammal is a human.

[0055] Una “cantidad eficaz” se refiere a una cantidad eficaz, a dosis y durante periodos de tiempo necesarios, para alcanzar el resultado terapéutico o profiláctico deseado. [0055] An "effective amount" refers to an amount effective, at doses and for periods of time necessary, to achieve the desired therapeutic or prophylactic result.

[0056] Una “cantidad terapéuticamente eficaz” de una sustancia/molécula de la invención puede variar según factores, tales como el estado de la enfermedad, edad, sexo y peso del individuo, y la capacidad de la sustancia/molécula para inducir una respuesta deseada en el individuo. Una cantidad terapéuticamente eficaz comprende una cantidad en la que cualquier efecto tóxico o perjudicial de la sustancia/molécula se ve superado por los efectos terapéuticamente beneficiosos. Una “cantidad profilácticamente eficaz” se refiere a una cantidad eficaz, a dosis y durante periodos de tiempo necesarios, para alcanzar el resultado profiláctico deseado. Habitualmente, pero no necesariamente, puesto que se usa una dosis profiláctica en sujetos antes o en una etapa más temprana de la enfermedad, la cantidad profilácticamente eficaz sería menor que la cantidad terapéuticamente eficaz. [0056] A "therapeutically effective amount" of a substance / molecule of the invention may vary according to factors, such as the disease status, age, sex and weight of the individual, and the ability of the substance / molecule to induce a response. desired in the individual. A therapeutically effective amount comprises an amount in which any toxic or harmful effect of the substance / molecule is overcome by the therapeutically beneficial effects. A "prophylactically effective amount" refers to an amount effective, at doses and for periods of time necessary, to achieve the desired prophylactic result. Usually, but not necessarily, since a prophylactic dose is used in subjects before or at an earlier stage of the disease, the prophylactically effective amount would be less than the therapeutically effective amount.

[0057] El término supervivencia a "largo plazo” se utiliza aquí para referirse a la supervivencia durante por lo menos 1 año, 5 años, 8 años o 10 años después del tratamiento terapéutico. [0057] The term "long-term survival" is used here to refer to survival for at least 1 year, 5 years, 8 years or 10 years after therapeutic treatment.

[0058] El término "resistencia incrementada" a un agente terapéutico u opción de tratamiento particular, cuando se utiliza según la presente invención, significa una respuesta disminuida a una dosis estándar del fármaco o un protocolo de tratamiento estándar. [0058] The term "increased resistance" to a particular therapeutic agent or treatment option, when used according to the present invention, means a diminished response to a standard dose of the drug or a standard treatment protocol.

[0059] El término "sensibilidad disminuida" a un agente terapéutico u opción de tratamiento particular, cuando se utiliza según la presente invención, significa una respuesta disminuida a una dosis estándar del agente o un protocolo de tratamiento estándar, donde la respuesta disminuida se puede compensar (al menos parcialmente) mediante el incremento de la dosis del agente, o la intensidad del tratamiento. [0059] The term " decreased sensitivity " to a particular therapeutic agent or treatment option, when used according to the present invention, means a diminished response to a standard dose of the agent or a standard treatment protocol, where the decreased response can be compensated (at least partially) by the increase of the dose of the agent, or the intensity of the treatment.

[0060] La "respuesta del paciente" se puede valorar utilizando cualquier punto final que indica un beneficio al paciente, incluyendo, sin limitación, (1) la inhibición, en cierto grado, del crecimiento del tumor, incluyendo la ralentización o detención completa del crecimiento; (2) reducción en el número células tumorales; (3) reducción en el tamaño del tumor; (4) inhibición (es decir, reducción, ralentización o detención completa) de la infiltración de células tumorales en órganos y/o tejidos periféricos adyacentes; (5) inhibición (es decir, reducción, ralentización o detención completa) de la metástasis; (6) aumento de la respuesta inmune antitumoral, que puede dar lugar, aunque no necesariamente, a la regresión o rechazo del tumor; (7) alivio, en cierto grado, de uno o más síntomas asociados con el tumor; (8) aumento del tiempo de supervivencia después del tratamiento; y/o (9) una mortalidad disminuida en un punto determinado de tiempo después del tratamiento. [0060] The "patient response" it can be assessed using any endpoint that indicates a benefit to the patient, including, without limitation, (1) the inhibition, to some extent, of tumor growth, including slowing or complete growth arrest; (2) reduction in the number of tumor cells; (3) reduction in tumor size; (4) inhibition (ie, reduction, slowdown or complete arrest) of infiltration of tumor cells in adjacent organs and / or peripheral tissues; (5) inhibition (ie reduction, slowdown or complete arrest) of metastasis; (6) increased antitumor immune response, which may lead, although not necessarily, to tumor regression or rejection; (7) relief, to some extent, of one or more symptoms associated with the tumor; (8) increased survival time after treatment; and / or (9) a decreased mortality at a certain point of time after treatment.

[0061] El término "antagonista" se utiliza en el sentido más amplio, e incluye cualquier molécula que parcial o totalmente inhibe o neutraliza una actividad biológica de un polipéptido, tal como PRO, o que inhibe parcial o totalmente la transcripción o traducción de un ácido nucleico que codifica el polipéptido. Entre las moléculas antagonistas se incluyen, pero sin limitación, anticuerpos antagonistas, fragmentos de polipéptidos, oligopéptidos, moléculas orgánicas (incluyendo moléculas pequeñas) y ácidos nucleicos no codificantes. [0061] The term " antagonist " it is used in the broadest sense, and includes any molecule that partially or totally inhibits or neutralizes a biological activity of a polypeptide, such as PRO, or that partially or totally inhibits the transcription or translation of a nucleic acid encoding the polypeptide. Antagonist molecules include, but are not limited to, antagonist antibodies, polypeptide fragments, oligopeptides, organic molecules (including small molecules) and non-coding nucleic acids.

[0062] El término "agonista" se utiliza en el sentido más amplio, e incluye cualquier molécula que parcial o totalmente mimetiza una actividad biológica de un polipéptido, tal como PRO, o que incrementa la transcripción o traducción de un ácido nucleico que codifica el polipéptido. Entre las moléculas agonistas se incluyen, pero sin limitación, anticuerpos agonistas, fragmentos de polipéptidos, oligopéptidos, moléculas orgánicas (incluyendo moléculas pequeñas), polinucleótidos PRO, polipéptidos PRO, y fusiones PRO-Fc. [0062] The term " agonist " it is used in the broadest sense, and includes any molecule that partially or totally mimics a biological activity of a polypeptide, such as PRO, or that increases the transcription or translation of a nucleic acid encoding the polypeptide. Agonist molecules include, but are not limited to, agonist antibodies, polypeptide fragments, oligopeptides, organic molecules (including small molecules), PRO polynucleotides, PRO polypeptides, and PRO-Fc fusions.

[0063] Un "agente terapéutico que reconoce un PRO o un polinucleótido de PRO" significa cualquier agente que afecta la expresión y/o actividad de PRO o un polinucleótido de PRO incluyendo, pero sin limitación, cualquiera de los agonistas o antagonistas de PRO descritos aquí, incluyendo agentes terapéuticos que ya son conocidos en la técnica, así como aquellos que se desarrollan posteriormente. [0063] A "therapeutic agent that recognizes a PRO or a polynucleotide of PRO" means any agent that affects the expression and / or activity of PRO or a PRO polynucleotide including, but not limited to, any of the PRO agonists or antagonists described herein, including therapeutic agents that are already known in the art, as well as those that They develop later.

[0064] El término “agente citotóxico”, tal como se utiliza aquí, se refiere a una sustancia que inhibe o previene una función celular y/o causa la muerte o destrucción celular. El término pretende incluir isótopos radiactivos (por ejemplo, At211, I131, I125, Y90, Re186, Re188, Sm153, Bi212, P32, Pb212 e isótopos radiactivos de Lu), agentes quimioterapéuticos (por ejemplo, metotrexato, adriamicina, alcaloides de la vinca (vincristina, vinblastina, etopósido), doxorrubicina, melfalán, mitomicina C, clorambucilo, daunorrubicina u otros agentes intercalantes, enzimas y fragmentos de las mismas, tales como enzimas nucleolíticas, antibióticos y toxinas, tales como toxinas que son moléculas pequeñas o toxinas enzimáticamente activas de origen bacteriano, fúngico, vegetal o animal, incluyendo fragmentos y/o variantes de las mismas, y los diversos agentes antitumorales o anticancerígenos descritos a continuación. A continuación se describen otros agentes citotóxicos. Un agente “tumoricida” causa la destrucción de las células tumorales. [0064] The term "cytotoxic agent", as used herein, refers to a substance that inhibits or prevents cellular function and / or causes cell death or destruction. The term is intended to include radioactive isotopes (for example, At211, I131, I125, Y90, Re186, Re188, Sm153, Bi212, P32, Pb212 and radioactive isotopes of Lu), chemotherapeutic agents (for example, methotrexate, adriamycin, vinca alkaloids (vincristine, vinblastine, etoposide), doxorubicin, melphalan, mitomycin C, chlorambucil, daunorubicin or other intercalating agents, enzymes and fragments thereof, such as nucleolytic enzymes, antibiotics and toxins, such as toxins that are small molecules or enzymatically active toxins of bacterial, fungal, plant or animal origin, including fragments and / or variants thereof, and the various antitumor or anticancer agents described below Other cytotoxic agents are described below A "tumoricidal" agent causes the destruction of cells Tumor

[0065] Una “toxina" es cualquier sustancia capaz de tener un efecto perjudicial sobre el crecimiento o proliferación de una célula. [0065] A "toxin" It is any substance capable of having a detrimental effect on the growth or proliferation of a cell.

[0066] Un "agente quimioterapéutico" es un compuesto químico útil en el tratamiento del cáncer. Los ejemplos de agentes quimioterapéuticos incluyen los agentes alquilantes tales como la tiotepa y la ciclofosfamida CYTOXAN®; los alquilsulfonatos tales como el busulfán, el improsulfán y el piposulfán; las aziridinas tales como la benzodopa, carboquone, meturedopa, y uredopa; las etileniminas y metilamelaminas, incluyendo la altretamina, trietilenmelamina, trietilenfosforamida, trietilentiofosforamida y trimetilolomelamina; las acetogeninas (especialmente la bullatacina y la bullatacinona); delta-9-tetrahidrocannabiol (dronabinol, MARINOL®); beta-lacona; lapacol; colquicinas; ácido betulínico; una camptotecina (incluyendo el análogo sintético topotecan(HYCAMTIN®), CPT-11 (irinotecan, CAMPTOSAR®), acetilcamptotecina, escopolectina y 9-aminocamptotecina); la briostatina; la calistatina; el CDC-1065 (incluyendo sus análogos sintéticos adozelesina, carzelesina y bizelesina); podofilotoxina; ácido podofílico; teniposide; las criptoficinas (particularmente la criptoficina 1 y la criptoficina 8); la dolastatina; la duocarmicina (incluyendo los análogos sintéticos, KW-2189 y CBI-TMI); la eleuterobina; la pancratistatina; una sarcodictiina; la espongistatina; las mostazas nitrogenadas tales como el clorambucilo, la clornafacina, la colofosfamida, la estramustina, la ifosfamida, la mecloretamina, el hidrocloruro del óxido de mecloretamina, el melfalán, la novembichina, la fenesterina, la prednimustina, la trofosfamida, la mostaza de uracilo; las nitrosureas tales como la carmustina, la clorozotocina, la fotemustina, la lomustina, la nimustina, y la ranimustina; los antibióticos tales como los antibióticos de enediina (por ejemplo, la caliqueamicina, especialmente la caliqueamicina gammaII y la caliqueamicina omegaII (véase, por ejemplo, Angew. Chem. Intl. Ed. Engl., 33:183-186 (1994); la dinemicina, inlcuyendo la dinemicina A; una esperamicina; así como el cromóforo de la neocarzinostatina y cromóforos de antibióticos de enedina cromoproteínas relacionadas), aclacinomisinas, actinomicina, autramicina, azaserina, bleomicinas, cactinomicina, carabicina, carminomicina, carzinofilina, cromomicinas, dactinomicina, daunorubicina, detorubicina, 6-diazo-5-oxo-L-norleucina, doxorubicina (Adriamicina®) (incluyendo la morfolino-doxorubicina, la cianomorfolino-doxorubicina, la 2-pirrolino-doxorubicina y la desoxidoxorubicina), la epirubicina, la esorubicina, la idarubicina, la marcelomicina, las mitomicinas tales como la mitomicina C, el ácido micofenólico, la nogalamicina, las olivomicinas, la peplomicina, la potfiromicina, la puromicina, la quelamicina, la rodorubicina, la estreptonigrina, la estreptozocina, la tubercidina, el ubenimex, la zinostatina, la zorubicina; los anti-metabolitos tales como el metotrexato y 5-fluorouracilo (5-FU); los análogos del ácido fólico tales como la denopterina, el metotrexato, la pteropterina, el trimetrexato; los análogos de purina tales como la fludarabina, la 6-mercaptopurina, la tiamiprina, la tioguanina; los análogos de pirimidina tales como la ancitabina, la azacitidina, la 6-azauridina, el carmofur, la citarabina, la didesoxiuridina, la doxifluridina, la enocitabina, la floxuridina; los andrógenos tales como la calusterona, el propionato de dromostanolona, el epitiostanol, la mepitiostana, la testolactona; los anti-adrenales tales como la aminoglutetimida, el mitotano, el trilostano; los rellenadores de ácido fólico tales como el ácido frolínico; la aceglatona; el glicósido de aldofosfamida; el ácido aminolevulínico; el eniluracilo; la amsacrina; el bestrabucilo; el bisantreno; el edatraxato; la defofamina; la demecolcina; la diaziquona; la elfomitina; el acetato de eliptinio; una epotilona; el etoglúcido; el nitrato de galio; la hidroxiurea; el lentinano; la lonidainina; los maitansinoides tales como la maitansina y las ansamitocinas; la mitoguazona; la mitoxantrona; el mopidanmol; la nitraerina; la pentostatina; el fenameto; la pirarubicina; la losoxantrona; la 2-etilhidrazida; la procarbazina; el complejo de polisacáridos PSK® (JHS Natural Products, Eugene, OR); la razoxana; la rizoxina; el sizofirano; el espirogermanio; el ácido tenuazónico; la triaziquona; la 2,2',2"-triclorotrietilamina; los tricotecenos (especialmente la toxina T-2, la verracurina A, la roridina A y la anguidina); el uretano; la vindesina (ELDISINA®, FILDESINA®); la dacarbazina; la manomustina; el mitobronitol; el mitolactol; el pipobromano; la gacitosina; el arabinósido ("Ara-C"); la tiotepa; los taxoides, por ejemplo, el paclitaxel TAXOL® (Bristol-Myers Squibb Oncology, Princeton, NJ), formulación en nanopartículas de paclitaxel diseñado en albúmina, libre de Cremóforos ABRAXANETM (American Pharmaceutical Partners, Schaumberg, Illinois), y el doxetaxel TAXOTERE® (Rhône-Poulenc Rorer, Antony, France); el cloranbucilo; la gemcitabina (Gemzar®); la 6-tioguanina; la mercaptopurina; el metotrexato; los análogos de platino tales como el cisplatino y carboplatino; la vinblastina (VELBAN®); el platino; el etopósido (VP-16); la ifosfamida; la mitoxantrona; la vincristina (ONCOVIN®); oxaliplatino; leucovovina; la vinorelbina (Navelbine®); la novantrona; el edatrexato; la daunomicina; la aminopterina; el ibandronato; el inhibidor de la topoisomerasa RFS 2000; la difluorometilornitina (DMFO); los retinoides tales como el ácido retinoico; la capecitabina (XELODA®); y las sales, ácidos o derivados farmacéuticamente aceptables de cualquiera de los anteriores; así como combinaciones de dos o más de los anteriores, tales como CHOP, una abreviación para una terapia combinada de ciclofosfamida, doxorubicina, vincristina y prednisolona y FOLFOX, una abreviación para una pauta de tratamiento con oxaliplatino (ELOXATINTM) combinado con 5-FU y leucovovina. [0066] A "chemotherapeutic agent" It is a chemical compound useful in the treatment of cancer. Examples of chemotherapeutic agents include alkylating agents such as thiotepa and CYTOXAN® cyclophosphamide; alkyl sulfonates such as busulfan, improsulfan and piposulfan; aziridines such as benzodopa, carboquone, meturedopa, and uredopa; ethyleneimines and methylamelamines, including altretamine, triethylenemelamine, triethylene phosphoramide, triethylenediophosphoramide and trimethylolomelamine; acetogenins (especially bullatacin and bullatacinone); delta-9-tetrahydrocannabiol (dronabinol, MARINOL®); beta-lacona; lapacol; colchicines; betulinic acid; a camptothecin (including the synthetic analogue topotecan (HYCAMTIN®), CPT-11 (irinotecan, CAMPTOSAR®), acetylcamptothecin, scopolectin and 9-aminocamptothecin); the biostatin; the calistatin; CDC-1065 (including its synthetic analogs adozelesin, carzelesin and bizelesin); podophyllotoxin; podophylic acid; teniposide; cryptophycins (particularly cryptophycin 1 and cryptophycin 8); dolastatin; duocarmycin (including synthetic analogs, KW-2189 and CBI-TMI); the eleuterobine; the pancratistatin; a sarcodictiin; the spongistatin; nitrogen mustards such as chlorambucil, chlornafacin, colophosphamide, estramustine, ifosfamide, mechlorethamine, mechlorethamine oxide hydrochloride, melphalan, novembichin, fenesterin, prednimustine, trophosphamide; nitrosureas such as carmustine, chlorozotocin, fotemustine, lomustine, nimustine, and ranimustine; antibiotics such as enediine antibiotics (for example, calicheamycin, especially gammaII caliqueamycin and omegaII caliqueamycin (see, for example, Angew. Chem. Intl. Ed. Engl., 33: 183-186 (1994); dynemycin, including dynemycin A; a speramycin; as well as the chromophore of neocarzinostatin and related chromophores of enedin antibiotics (chromoproteins), clarcinomysins, actinomycin, autramycin, azaserine, bleomycins, cactinomycin, carabicin, carminomycin, chromomycin, caromycinin, chromicorin, chromicorin, chromicorin , detorubicin, 6-diazo-5-oxo-L-norleucine, doxorubicin (Adriamycin®) (including morpholino-doxorubicin, cyanomorpholino-doxorubicin, 2-pyrrolino-doxorubicin and deoxy oxubicin), epirubicin, esirubicin, esirubicin idarubicin, marcelomycin, mitomycins such as mitomycin C, mycophenolic acid, nogalamicin, olivomycins, peplomycin, potfiromycin, puromycin, chelamicin, rodorubicin, streptonigrin, streptozocin, tubercidin, ubenimex, zinostatin, zorubicin; anti-metabolites such as methotrexate and 5-fluorouracil (5-FU); folic acid analogs such as denopterin, methotrexate, pteropterin, trimetrexate; purine analogs such as fludarabine, 6-mercaptopurine, thiamiprine, thioguanine; pyrimidine analogues such as ancitabine, azacitidine, 6-azauridine, carmofur, cytarabine, dideoxyuridine, doxifluridine, enocitabine, floxuridine; androgens such as calusterone, dromostanolone propionate, epitiostanol, mepitiostana, testolactone; anti-adrenal drugs such as aminoglutethimide, mitotane, trilostane; folic acid fillers such as frolinic acid; aceglatone; aldofosfamide glycoside; aminolevulinic acid; the eniluracil; the amsacrine; the bestrabucilo; the bisantrene; edatraxate; defofamine; demecolcin; the diaziquone; elfomitin; elliptinium acetate; an epothilone; the etoglucid; gallium nitrate; hydroxyurea; the lentinano; lonidainin; maitansinoids such as maitansin and ansamitocins; the mitoguazone; mitoxantrone; mopidanmol; nitraerine; pentostatin; the fenameto; pyrarubicin; losoxantrone; 2-ethylhydrazide; procarbazine; the PSK® polysaccharide complex (JHS Natural Products, Eugene, OR); the razoxana; rhizoxin; the sizofirano; the spirogermanium; tenuazonic acid; the triaziquone; 2,2 ', 2 "-trichlorotriethylamine; trichothecenes (especially T-2 toxin, verracurin A, roridine A and anguidine); urethane; vindesine (ELDISINA®, FILDESINA®); dacarbazine; the manomustine; the mitobronitol; the mitolactol; the pipobroman; the gacitosina; the arabinoside ("Ara-C"); the thiotepa; taxoids, for example, paclitaxel TAXOL® (Bristol-Myers Squibb Oncology, Princeton, NJ), an albumin-designed paclitaxel nanoparticle formulation, free of ABRAXANETM (American Pharmaceutical Partners, Schaumberg, Illinois) Cremophors, and TAXOTERE® doxetaxel (Rhône-Poulenc Rorer, Antony, France); chlorabucil; gemcitabine (Gemzar®); 6-thioguanine; mercaptopurine; methotrexate; platinum analogs such as cisplatin and carboplatin; vinblastine (VELBAN®); the platinum; the etoposide (VP-16); ifosfamide; mitoxantrone; vincristine (ONCOVIN®); oxaliplatin; leucovovine; vinorelbine (Navelbine®); novantrone; edatrexate; daunomycin; the aminopterin; ibandronate; the topoisomerase inhibitor RFS 2000; difluoromethylornitine (DMFO); retinoids such as retinoic acid; capecitabine (XELODA®); and pharmaceutically acceptable salts, acids or derivatives of any of the foregoing; as well as combinations of two or more of the above, such as CHOP, an abbreviation for a combined therapy of cyclophosphamide, doxorubicin, vincristine and prednisolone and FOLFOX, an abbreviation for an oxaliplatin (ELOXATINTM) treatment regimen combined with 5-FU and leucovovine

[0067] También se incluyen en esta definición agentes antihormonales que actúan para regular, reducir, bloquear o inhibir los efectos de hormonas que pueden promover el crecimiento del cáncer y, a menudo, están en forma de tratamiento sistémico, o para el cuerpo completo. Pueden ser hormonas ellos mismos. Entre los ejemplos se incluyen antiestrógenos y moduladores selectivos de los receptores de estrógenos (SERM) incluyendo, por ejemplo, tamoxifeno (incluyendo tamoxifeno de NOLVADEX®), raloxifeno EVISTA®, droloxifeno, 4-hidroxitamoxifeno, trioxifeno, keoxifeno, LY117018, onapristona y toremifeno FARESTON®; antiprogesteronas; reguladores por disminución de los receptores de estrógenos (ERD); agentes que actúan para suprimir o anular las funciones de los ovarios, por ejemplo, agonistas de la hormona liberadora de la hormona luteinizante (LHRH), tales como acetato de leuprólido LUPRON® y ELIGARD®, acetato de goserelina, acetato de buserelina y tripterelina; otros antiandrógenos, tales como flutamida, nilutamida y bicalutamida; e inhibidores de la aromatasa que inhiben la enzima aromatasa, los que regulan la producción de estrógenos en las glándulas adrenales, tales como, por ejemplo 4(5)-imidazoles, aminoglutetimida, acetato de megestrol MEGASE®, exemestano AROMASIN®, formestano, fadrozol, vorozol RNISOR®, letrozol FEMARA® y anastrozol ARIMIDEX®. Además, dicha definición de agentes quimioterapéuticos incluye bisfosfonatos, tales como clodronato (por ejemplo, BONEFOS® o OSTAC®), etidronato DIDROCAL®, NE58095, ácido zoledrónico/zoledronato ZOMETA®, alendronato FOSAMAX®, pamidronato AREDIA®, tiludronato SKELID® o risedronato ACTONEL®; así como troxacitabina (un análogo del nucleósido de citosina 1,3-dioxolano); oligonucleótidos antisentido, especialmente aquellos que inhiben la expresión de los genes de las rutas de señalización implicados en la proliferación de células aberrantes, tales como por ejemplo, alfa-PKC, Raf, H-Ras y el receptor del factor de crecimiento epidérmico (EGF-R); vacunas, tales como la vacuna THERATOPE® y vacunas de terapia génica, por ejemplo, vacuna ALLOVECTIN®, vacuna LEUVECTIN® y vacuna VAXID®; inhibidor de la topoisomerasa 1 LURTOTECAN®; ABARELIX® rmRH; lapatinib ditosilato (una pequeña molécula inhibidora de la tirosina quinasa dual ErbB-2 y EGFR también conocida como GW572016); y sales, ácidos o derivados farmacéuticamente aceptables de cualquiera de los anteriores. [0067] Also included in this definition are anti-hormonal agents that act to regulate, reduce, block or inhibit the effects of hormones that can promote cancer growth and are often in the form of systemic treatment, or for the whole body. They can be hormones themselves. Examples include antiestrogens and estrogen receptor selective modulators (SERMs) including, for example, tamoxifen (including NOLVADEX® tamoxifen), raloxifene EVISTA®, droloxifene, 4-hydroxytyamoxyphene, trioxifene, keoxifen, LY117018 and toremiphene FARESTON®; antiprogesterones; estrogen receptor decrease (ERD) regulators; agents that act to suppress or nullify the functions of the ovaries, for example, luteinizing hormone releasing hormone (LHRH) agonists, such as LUPRON® and ELIGARD® leuprólido acetate, goserelin acetate, buserelin acetate and tripterelin; other antiandrogens, such as flutamide, nilutamide and bicalutamide; and aromatase inhibitors that inhibit the enzyme aromatase, which regulate the production of estrogens in the adrenal glands, such as, for example, 4 (5) -imidazoles, aminoglutethimide, MEGASE® megestrol acetate, AROMASIN® exemestane, formestane, fadrozol , RNISOR® vorozole, FEMARA® letrozole and ARIMIDEX® anastrozole. Furthermore, said definition of chemotherapeutic agents includes bisphosphonates, such as clodronate (for example, BONEFOS® or OSTAC®), DIDROCAL® etidronate, NE58095, zoledronic acid / zoledronate ZOMETA®, alendronate FOSAMAX®, pamidronate AREDIA®, tiludronate SKEL tiludronate odoledronate ACTONEL®; as well as troxacitabine (an analogue of the cytosine 1,3-dioxolane nucleoside); antisense oligonucleotides, especially those that inhibit the expression of the signaling pathway genes involved in the proliferation of aberrant cells, such as, for example, alpha-PKC, Raf, H-Ras and the epidermal growth factor receptor (EGF- R); vaccines, such as the THERATOPE® vaccine and gene therapy vaccines, for example, ALLOVECTIN® vaccine, LEUVECTIN® vaccine and VAXID® vaccine; LURTOTECAN® topoisomerase 1 inhibitor; ABARELIX® rmRH; lapatinib ditosylate (a small molecule tyrosine kinase dual inhibitor ErbB-2 and EGFR also known as GW572016); and pharmaceutically acceptable salts, acids or derivatives of any of the foregoing.

[0068] Un "agente inhibidor del crecimiento", cuando se usa aquí, se refiere a un compuesto o composición que inhibe el crecimiento de una célula (tal como una célula que expresa PRO) in vitro o in vivo. Por tanto, el agente inhibidor del crecimiento puede ser aquel que reduzca significativamente el porcentaje de células (tales como una célula que expresa PRO) en fase S. Entre los ejemplos de agentes inhibidores del crecimiento se incluyen agentes que bloquean la progresión del ciclo celular (en un lugar distinto a la fase S), tales como agentes que inducen la detención en G1 y la detención en fase M. Entre los bloqueantes de la fase-M clásicos se incluyen los derivados de la vinca (vincristina y vinblastina), taxanos e inhibidores de la topoisomerasa II, tales como doxorrubicina, epirrubicina, daunorrubicina, etopósido y bleomicina. Aquellos agentes que detienen el ciclo celular en la fase G1 también afectan a la detención en fase S, por ejemplo, agentes alquilantes de ADN, tales como tamoxifeno, prednisona, dacarbazina, mecloretamina, cisplatino, metotrexato, 5-fluorouracilo y ara-C. Puede encontrarse información adicional en The Molecular Basis of Cancer, Mendelsohn e Israel, eds., Capítulo 1, titulado “Cell cycle regulation, oncogenes, and antineoplastic drugs" de Murakami et al. (WB Saunders: Philadelphia, 1995), especialmente la pág. 13. Los taxanos (paclitaxel y docetaxel) son fármacos anticancerígenos derivados ambos del tejo. El docetaxel (TAXOTERE®, Rhone-Poulenc Rorer), derivado del tejo europeo, es un análogo semisintético de paclitaxel (TAXOL®, Bristol-Myers Squibb). El paclitaxel y el docetaxel promueven el ensamblaje de microtúbulos a partir de dímeros de tubulina y estabilizan los microtúbulos previniendo la despolimerización, lo que da lugar a la inhibición de la mitosis celular. [0068] A "growth inhibitory agent" when used herein refers to a compound or composition that inhibits the growth of a cell (such as a cell expressing PRO) in vitro or in vivo. Therefore, the growth inhibiting agent can be one that significantly reduces the percentage of cells (such as a cell expressing PRO) in S phase. Examples of growth inhibiting agents include agents that block cell cycle progression ( in a place other than phase S), such as agents that induce G1 arrest and phase M arrest. Classical M-phase blockers include those derived from vinca (vincristine and vinblastine), taxanes and topoisomerase II inhibitors, such as doxorubicin, epirubicin, daunorubicin, etoposide and bleomycin. Those agents that stop the cell cycle in the G1 phase also affect S-phase arrest, for example, DNA alkylating agents, such as tamoxifen, prednisone, dacarbazine, mechlorethamine, cisplatin, methotrexate, 5-fluorouracil and ara-C. Additional information can be found in The Molecular Basis of Cancer, Mendelsohn and Israel, eds., Chapter 1, entitled “Cell cycle regulation, oncogenes, and antineoplastic drugs " from Murakami et al. (WB Saunders: Philadelphia, 1995), especially p. 13. Taxanes (paclitaxel and docetaxel) are anticancer drugs both derived from yew. Docetaxel (TAXOTERE®, Rhone-Poulenc Rorer), derived from European yew, is a semi-synthetic paclitaxel analogue (TAXOL®, Bristol-Myers Squibb). Paclitaxel and docetaxel promote the assembly of microtubules from tubulin dimers and stabilize the microtubules preventing depolymerization, which results in the inhibition of cell mitosis.

[0069] Tal como se utiliza aquí, el término “inhibidor de EGFR” se refiere a compuestos que se unen o en cualquier caso interaccionan directamente con EGFR y evitan o reducen su actividad de señalización, y es referido alternativamente como un “antagonista de EGFR”. Entre los ejemplos de dichos agentes se incluyen anticuerpos y moléculas pequeñas que se unen a EGFR. Ejemplos de anticuerpos que se unen a EGFR incluyen MAb 579 (ATCC CRL HB 8506), MAb 455 (ATCC CRL HB8507), MAb 225 (ATCC CRL 8508), MAb 528 (ATCC CRL 8509) (véase la patente de Estados Unidos No. 4.943. 533, Mendelsohn et al.) y variantes de los mismos, tales como 225 quimerizado (C225 o Cetuximab; ERBUTIX®) y 225 humano reconformado (H225) (véase, WO 96/40210, Imclone Systems Inc.); IMC-11 F8, un anticuerpo dirigido a EGFR completamente humano (Imclone); anticuerpos que se unen a EGFR mutante de tipo II (Patente de Estados Unidos No. 5,212,290); anticuerpos humanizados y quiméricos que se unen a EGFR tal como se describen en la Patente de Estados Unidos No. 5.891.996; y anticuerpos humanos que se unen a EGFR, tales como ABX-EGF o Panitumumab (véase WO98/50433, Abgenix/Amgen); EMD 55900 (Stragliotto et al. Eur. J. Cancer 32A:636-640 (1996)); EMD7200 (matuzumab), un anticuerpo de EGFR humanizado dirigido contra EGFR que compite con EGF y TGF-alfa por la unión a EGFR (EMD/Merck); anticuerpo de EGFR humano, HuMax-EGFR (GenMab); anticuerpos totalmente humanos conocidos como E1.1, E2.4, E2.5, E6.2, E6.4, E2.11, E6. 3 y E7.6. 3 y descritos en la patente de Estados Unidos 6.235.883; MDX-447 (Medarex Inc); y mAb 806 o mAb 806 humanizado (Johns et al., J. Biol. Chem. 279(29):30375-30384 (2004)). El anticuerpo anti-EGFR se puede conjugar con un agente citotóxico, generando así un inmunoconjugado (véase, por ekemplo, EP659,439A2, Merck Patent GmbH). Los antagonistas de EGFR incluyen moléculas pequeñas, tales como compuestos descritos en las Patentes de Estados Unidos Nos: 5,616,582, 5,457,105, 5,475,001, 5,654,307, 5,679,683, 6,084,095, 6,265,410, 6,455,534, 6,521,620, 6,596,726, 6,713,484, 5,770,599, 6,140,332, 5,866,572, 6,399,602, 6,344,459, 6,602,863, 6,391,874, 6,344,455, 5,760,041, 6,002,008, y 5,747,498, así como las siguientes publicaciones PCT: WO98/14451, WO98/50038, WO99/09016, y WO99/24037. Los antagonistas de EGFR de molécula pequeña particulares incluyen OSI-774 (CP-358774, erlotinib, TARCEVA® Genentech/OSI Pharmaceuticals); PD 183805 (CI 1033, 2-propenamida, N-[4-[(3-cloro-4-fluorofenil)amino]-7-[3-(4-morfolinil)propoxi]-6-quinazolinil]-, diclorhidrato, Pfizer Inc.); ZD1839, gefitinib (IRESSA™) 4-(3’-Cloro-4’-fluoroanilino)-7-metoxi-6-(3-morfolinopropoxi) quinazolina, AstraZeneca); ZM 105180 ((6-amino-4-(3-metilfenil-amino)-quinazolina, Zeneca); BIBX-1382 (N8-(3-cloro-4-fluoro-fenil)-N2-(1-metilpiperidin-4-il)-pirimido[5,4-d]pirimidina-2,8-diamina, Boehringer Ingelheim); PKI-166 ((R)-4-[4-[(1-feniletil) amino]-1Hpirrolo[2,3-d]pirimidin-6-il]-fenol); (R)-6-(4-hidroxifenil)- 4-[(1-feniletil)amino]-7H-pirrolo[2,3-d]pirimidina); CL-387785 (N-[4-[(3-bromofenil) amino]-6-quinazolinil]-2-butinamida); EKB-569 (N-[4-[(3-cloro-4- fluorofenil) amino]- 3-ciano-7etoxi- 6- quinolinil]- 4-(dimetilamino)- 2- butenamida) (Wyeth); AG1478 (Pfizer); AG 1571 (SU 5271; Pfizer); inhibidores de tirosina quinasa duales EGFR/HER2, tales como lapatinib (TYKERB®, GSK572016 o N-[3-cloro-4-[(3fluorofenil) metoxi]fenil]6[5[[ [2-metilsulfonil) etil] amino] metil]- 2- furanil]- 4- quinazolinamina; Glaxo-SmithKline). [0069] As used herein, the term "EGFR inhibitor" refers to compounds that bind or in any case interact directly with EGFR and prevent or reduce their signaling activity, and is alternatively referred to as an "EGFR antagonist. " Examples of such agents include antibodies and small molecules that bind to EGFR. Examples of antibodies that bind to EGFR include MAb 579 (ATCC CRL HB 8506), MAb 455 (ATCC CRL HB8507), MAb 225 (ATCC CRL 8508), MAb 528 (ATCC CRL 8509) (see U.S. Patent No. 4,943, 533, Mendelsohn et al.) And variants thereof, such as 225 chimerized (C225 or Cetuximab; ERBUTIX®) and 225 reconstituted human (H225) (see, WO 96/40210, Imclone Systems Inc.); IMC-11 F8, an antibody directed to fully human EGFR (Imclone); antibodies that bind mutant EGFR type II (US Patent No. 5,212,290); humanized and chimeric antibodies that bind to EGFR as described in US Patent No. 5,891,996; and human antibodies that bind to EGFR, such as ABX-EGF or Panitumumab (see WO98 / 50433, Abgenix / Amgen); EMD 55900 (Stragliotto et al. Eur. J. Cancer 32A: 636-640 (1996)); EMD7200 (matuzumab), a humanized EGFR antibody directed against EGFR that competes with EGF and TGF-alpha for binding to EGFR (EMD / Merck); human EGFR antibody, HuMax-EGFR (GenMab); fully human antibodies known as E1.1, E2.4, E2.5, E6.2, E6.4, E2.11, E6. 3 and E7.6. 3 and described in US Patent 6,235,883; MDX-447 (Medarex Inc); and mAb 806 or mAb 806 humanized (Johns et al., J. Biol. Chem. 279 (29): 30375-30384 (2004)). The anti-EGFR antibody can be conjugated with a cytotoxic agent, thereby generating an immunoconjugate (see, for example, EP659,439A2, Merck Patent GmbH). EGFR antagonists include small molecules, such as compounds described in US Pat. Nos: 5,616,582, 5,457,105, 5,475,001, 5,654,307, 5,679,683, 6,084,095, 6,265,410, 6,455,534, 6,521,620, 6,596,726, 6,713,484, 5,770,599, 6,140,399, 6,140,399, 6,140,399, 6,140,399, 6,140,392, 6,140,399, 6,140,399, 6,140,399, 6,140,399, 6,140,399, 6,140,399, 6,140,399, 6,140,399, 6,140,399, 6,140,392, 6,340,599, 6,140,392 6,344,459, 6,602,863, 6,391,874, 6,344,455, 5,760,041, 6,002,008, and 5,747,498, as well as the following PCT publications: WO98 / 14451, WO98 / 50038, WO99 / 09016, and WO99 / 24037. Particular small molecule EGFR antagonists include OSI-774 (CP-358774, erlotinib, TARCEVA® Genentech / OSI Pharmaceuticals); PD 183805 (CI 1033, 2-propenamide, N- [4 - [(3-chloro-4-fluorophenyl) amino] -7- [3- (4-morpholinyl) propoxy] -6-quinazolinyl] -, dihydrochloride, Pfizer Inc.); ZD1839, gefitinib (IRESSA ™) 4- (3’-Chloro-4’-fluoroanilino) -7-methoxy-6- (3-morpholinopropoxy) quinazoline, AstraZeneca); ZM 105180 ((6-amino-4- (3-methylphenyl-amino) -quinazoline, Zeneca); BIBX-1382 (N8- (3-chloro-4-fluoro-phenyl) -N2- (1-methylpiperidin-4- il) -pyrimido [5,4-d] pyrimidine-2,8-diamine, Boehringer Ingelheim); PKI-166 ((R) -4- [4 - [(1-phenylethyl) amino] -1Hpyrrolo [2,3 -d] pyrimidin-6-yl] -phenol); (R) -6- (4-hydroxyphenyl) -4 - [(1-phenylethyl) amino] -7H-pyrrolo [2,3-d] pyrimidine); CL-387785 (N- [4 - [(3-bromophenyl) amino] -6-quinazolinyl] -2-butinamide); EKB-569 (N- [4 - [(3-chloro-4-fluorophenyl) amino] -3-cyano-7-ethoxy-6- quinolinyl] -4- (dimethylamino) -2-butenamide) (Wyeth); AG1478 (Pfizer); AG 1571 (SU 5271; Pfizer); dual EGFR / HER2 tyrosine kinase inhibitors, such as lapatinib (TYKERB®, GSK572016 or N- [3-chloro-4 - [(3fluorophenyl) methoxy] phenyl] 6 [5 [[[2-methylsulfonyl) ethyl] amino] methyl ] -2-furanyl] -4-quinazolinamine; Glaxo-SmithKline).

[0070] Un “inhibidor de tirosina quinasa” es una molécula que inhibe la actividad de tirosina quinasa de una tirosina quinasa, tal como un receptor HER. Ejemplos de dichos inhibidores incluyen los fármacos dirigidos a EGFR indicados en el párrafo anterior; inhibidor de tirosina quinasa de HER2 de molécula pequeña, tal como TAK165 disponible en Takeda; CP-724,714, un inhibidor selectivo oral del receptor tirosina quinasa ErbB2 (Pfizer y OSI); inhibidores de HER duales, tales como EKB-569 (disponible de Wyeth) que se unen preferiblemente a EGFR, pero inhiben las células que sobreexpresan tanto HER2 como EGFR; lapatinib (GSK572016; disponible de Glaxo-SmithKline), un inhibidor oral de tirosina quinasa de HER2 y EGFR; PKI-166 (disponible de Novartis); inhibidores pan-HER, tales como canertinib (CI-1033; Pharmacia); inhibidores Raf-1, tales como agente antisentido ISIS-5132 disponible de ISIS Pharmaceuticals que inhiben la señalización de Raf-1; inhibidores de TK no dirigidos a HER, tales como mesilato de imatinib (GLEEVEC™, disponible de Glaxo SmithKline); inhibidores de tirosina quinasa multidirigidos, tales como sunitinib (SUTENT®, disponible de Pfizer); inhibidores de tirosina quina de receptor de VEGF, tales como vatalanib (PTK787/ZK222584, disponible de Novartis/Schering AG); inhibidor CI-1040 de quinasa I regulada por MAPK extracelular (disponible de Pharmacia); quinazolinas, tales como PD 153035,4-(3-cloroanilino) quinazolina; piridopirimidinas; pirimidopirimidinas; pirrolopirimidinas, tales como CGP 59326, CGP 60261 y CGP 62706; pirazolopirimidinas, 4-(fenilamino)-7H-pirrolo[2,3-d] pirimidinas; curcumina (diferuloil metano, 4,5-bis (4fluoroanilino)ftalimida); tirfostinas que contienen grupos nitrotiofeno; PD-0183805 (Warner-Lambert); moléculas antisentido (por ejemplo, las que se unen a ácido nucleico que codifica HER); quinoxalinas (Patente de Estados Unidos No. 5,804,396); trifostinas (Patente de Estados Unidos No. 5,804,396); ZD6474 (Astra Zeneca); PTK-787 (Novartis/Schering AG); inhibidores pan-HER, tales como CI-1033 (Pfizer); Affinitac (ISIS 3521; Isis/Lilly); mesilato de imatinib (GLEEVEC™); PKI 166 (Novartis); GW2016 (Glaxo SmithKline); CI-1033 (Pfizer); EKB-569 (Wyeth); Semaxinib (Pfizer); ZD6474 (AstraZeneca); PTK-787 (Novartis/Schering AG); INC-1C11 (Imclone); o tal como se describr en cualquira de las siguientes publicaciones de patentes: Patente de Estados Unidos No. 5,804,396; WO 1999/09016 (American Cyanamid); WO 1998/43960 (American Cyanamid); WO 1997/38983 (Warner Lambert); WO 1999/06378 (Warner Lambert); WO 1999/06396 (Warner Lambert); WO 1996/30347 (Pfizer, Inc); WO 1996/33978 (Zeneca); WO 1996/3397 (Zeneca); y WO 1996/33980 (Zeneca). [0070] A "tyrosine kinase inhibitor" is a molecule that inhibits the tyrosine kinase activity of a tyrosine kinase, such as an HER receptor. Examples of such inhibitors include the drugs directed to EGFR indicated in the preceding paragraph; small molecule HER2 tyrosine kinase inhibitor, such as TAK165 available from Takeda; CP-724,714, an oral selective tyrosine kinase receptor inhibitor ErbB2 (Pfizer and OSI); dual HER inhibitors, such as EKB-569 (available from Wyeth) that preferentially bind to EGFR, but inhibit cells that overexpress both HER2 and EGFR; lapatinib (GSK572016; available from Glaxo-SmithKline), an oral tyrosine kinase inhibitor of HER2 and EGFR; PKI-166 (available from Novartis); pan-HER inhibitors, such as canertinib (CI-1033; Pharmacia); Raf-1 inhibitors, such as ISIS-5132 antisense agent available from ISIS Pharmaceuticals that inhibit Raf-1 signaling; non-HER-directed TK inhibitors, such as imatinib mesylate (GLEEVEC ™, available from Glaxo SmithKline); multidirected tyrosine kinase inhibitors, such as sunitinib (SUTENT®, available from Pfizer); VEGF receptor tyrosine kin inhibitors, such as vatalanib (PTK787 / ZK222584, available from Novartis / Schering AG); CI-1040 kinase I inhibitor regulated by extracellular MAPK (available from Pharmacia); quinazolines, such as PD 153035,4- (3-chloroanilino) quinazoline; pyridopyrimidines; pyrimidopyrimidines; pyrrolopyrimidines, such as CGP 59326, CGP 60261 and CGP 62706; pyrazolopyrimidines, 4- (phenylamino) -7H-pyrrolo [2,3-d] pyrimidines; curcumin (diferuloyl methane, 4,5-bis (4fluoroanilino) phthalimide); thyrostins containing nitrotiophene groups; PD-0183805 (Warner-Lambert); antisense molecules (for example, those that bind to nucleic acid encoding HER); quinoxalines (U.S. Patent No. 5,804,396); trifostines (U.S. Patent No. 5,804,396); ZD6474 (Astra Zeneca); PTK-787 (Novartis / Schering AG); pan-HER inhibitors, such as CI-1033 (Pfizer); Affinitac (ISIS 3521; Isis / Lilly); Imatinib Mesylate (GLEEVEC ™); PKI 166 (Novartis); GW2016 (Glaxo SmithKline); CI-1033 (Pfizer); EKB-569 (Wyeth); Semaxinib (Pfizer); ZD6474 (AstraZeneca); PTK-787 (Novartis / Schering AG); INC-1C11 (Imclone); or as described in any of the following patent publications: US Patent No. 5,804,396; WO 1999/09016 (American Cyanamid); WO 1998/43960 (American Cyanamid); WO 1997/38983 (Warner Lambert); WO 1999/06378 (Warner Lambert); WO 1999/06396 (Warner Lambert); WO 1996/30347 (Pfizer, Inc); WO 1996/33978 (Zeneca); WO 1996/3397 (Zeneca); and WO 1996/33980 (Zeneca).

[0071] "Anticuerpos" (Abs) e "inmunoglobulinas" (Igs) se refieren a glicoproteínas que tienen características estructurales similares. Aunque los anticuerpos muestran especificidad de unión a un antígeno específico, las inmunoglobulinas incluyen tanto anticuerpos como otras moléculas parecidas a anticuerpos que carecen generalmente de especificidad a antígeno. Los polipéptidos del último tipo se producen, por ejemplo, a niveles bajos por el sistema linfático y a niveles incrementados por mielomas. [0071] "Antibodies" (Abs) e "immunoglobulins" (Igs) refer to glycoproteins that have similar structural characteristics. Although antibodies show specificity of binding to a specific antigen, immunoglobulins include both antibodies and other antibody-like molecules that generally lack antigen specificity. Polypeptides of the latter type are produced, for example, at low levels by the lymphatic system and at levels increased by myelomas.

[0072] Los términos "anticuerpo" e "inmunoglobulina" se utilizan indistintamente en el sentido más amplio e incluyen anticuerpos monoclonales (por ejemplo, anticuerpos monoclonales de longitud completa o intactos), anticuerpos policlonales, anticuerpos monovalentes, anticuerpos multivalentes, anticuerpos multiespecíficos (por ejemplo, anticuerpos biespecíficos, siempre que muestren la actividad biológica deseada), y también pueden incluir ciertos fragmentos de anticuerpos (tal como se describe en detalle aquí). Un anticuerpo puede ser quimérico, humano, humanizado y/o madurado para afinidad. [0072] The terms "antibody" e "immunoglobulin" they are used interchangeably in the broadest sense and include monoclonal antibodies (for example, full-length or intact monoclonal antibodies), polyclonal antibodies, monovalent antibodies, multivalent antibodies, multispecific antibodies (e.g. bispecific antibodies, as long as they show the desired biological activity ), and may also include certain antibody fragments (as described in detail here). An antibody can be chimeric, human, humanized and / or matured for affinity.

[0073] El término "anticuerpo anti-PRO" o "un anticuerpo que se une a PRO" se refiere a un anticuerpo que es capaz de unirse a PRO con suficiente afinidad de manera que el anticuerpo es útil como agente de diagnóstico y/o terapéutico en el reconocimiento de PRO. Preferiblemente, el grado de unión de un anticuerpo anti-PRO a una proteína no PRO no relacionada es inferior a aproximadamente el 10% de la unión del anticuerpo a PRO medida, por ejemplo, mediante un radioinmunoensayo (RIA). En ciertas realizaciones, un anticuerpo que se une a PRO tiene una constante de disociación (Kd) de: 1 !M, : 100 nM, : 10 nM, : 1 nM, o : 0,1 nM. En ciertas realizaciones, un anticuerpo anti-PRO se une a un epítopo de PRO que se conserva entre PRO de diferentes especies. [0073] The term "anti-PRO antibody" or "an antibody that binds to PRO" refers to an antibody that is capable of binding PRO with sufficient affinity so that the antibody is useful as a diagnostic and / or therapeutic agent in the recognition of PRO. Preferably, the degree of binding of an anti-PRO antibody to an unrelated non-PRO protein is less than about 10% of the binding of the antibody to PRO measured, for example, by a radioimmunoassay (RIA). In certain embodiments, an antibody that binds to PRO has a dissociation constant (Kd) of: 1 µM,: 100 nM,: 10 nM,: 1 nM, or: 0.1 nM. In certain embodiments, an anti-PRO antibody binds to a PRO epitope that is conserved between PROs of different species.

[0074] Los términos "anticuerpo de longitud completa," "anticuerpo intacto" y "anticuerpo completo" se utilizan aquí indistintamente para referirse a un anticuerpo en su forma sustancialmente intacta, no a fragmentos de anticuerpo tal como se define a continuación. Los términos se refieren particularmente a un anticuerpo con cadenas pesadas que contienen la región Fc. [0074] The terms "full length antibody," "intact antibody" and "complete antibody" they are used interchangeably herein to refer to an antibody in its substantially intact form, not antibody fragments as defined below. The terms particularly refer to an antibody with heavy chains containing the Fc region.

[0075] El término “fragmentos de anticuerpo” comprende una porción de un anticuerpo intacto, preferiblemente comprende la región del mismo de unión a antígeno. Algunos ejemplos de fragmentos de anticuerpo incluyen fragmentos Fab, Fab’, F(ab’)2, y Fv; diabodies; anticuerpos lineales; moléculas de anticuerpos de cadena única; y anticuerpos multiespecíficos formados a partir de fragmentos de anticuerpos [0075] The term "antibody fragments" comprises a portion of an intact antibody, preferably comprising the antigen-binding region thereof. Some examples of antibody fragments include Fab, Fab ’, F (ab’) 2, and Fv fragments; diabodies; linear antibodies; single chain antibody molecules; and multispecific antibodies formed from antibody fragments

[0076] La digestión de anticuerpos con papaína produce dos fragmentos de unión a antígeno idénticos, denominados fragmentos “Fab”, cada uno de los cuales posee un único sitio de unión a antígeno, y un fragmento “Fc” residual, cuyo nombre refleja su capacidad de cristalizar fácilmente. El tratamiento con pepsina produce un fragmento F(ab’)2 que tiene dos sitios de combinación a antígeno y que incluso es capaz de entrecruzar el antígeno. [0076] Antibody digestion with papain produces two identical antigen-binding fragments, called "Fab" fragments, each of which has a single antigen-binding site, and a residual "Fc" fragment, whose name reflects its ability to crystallize easily. Pepsin treatment produces an F (ab ’) 2 fragment that has two antigen combination sites and is even capable of cross-linking the antigen.

[0077] “Fv” es el fragmento mínimo de anticuerpo que contiene un sitio completo de unión a antígeno. En una realización, una especie de FC de dos cadenas consiste en un dímero de un dominio variable de cadena pesada y uno de cadena ligera en asociación estrecha no covalente. Colectivamente, las seis CDR de una Fv confieren al anticuerpo una especificidad de unión a antígeno. Sin embargo, incluso un único dominio variable (o la mitad de una Fv que comprende sólo tres CDR específicas de antígeno) tiene la capacidad de reconocer y unirse a antígeno, aunque con una menor afinidad que el sitio de unión completo. [0077] "Fv" is the minimum antibody fragment that contains a complete antigen binding site. In one embodiment, a two-chain FC species consists of a dimer of a heavy chain and a light chain variable domain in close non-covalent association. Collectively, the six CDRs of an Fv give the antibody an antigen binding specificity. However, even a single variable domain (or half of an Fv comprising only three antigen-specific CDRs) has the ability to recognize and bind antigen, although with a lower affinity than the complete binding site.

[0078] El fragmento Fab contiene los dominios variables de cadena pesada y cadena ligera y también contiene el dominio constante de la cadena ligera y el primer dominio constante (CH1) de la cadena pesada. Los fragmentos Fab’ difieren de los fragmentos Fab por la adición de una serie de residuos en el extremo carboxi terminal del dominio CH1 de la cadena pesada que incluyen una o más cisteínas de la región bisagra del anticuerpo. Fab’-SH es la denominación en la presente invención para Fab’ en el que el residuo o residuos de cisteína de los dominios constantes transportan un grupo tiol libre. Los fragmentos de anticuerpos F(ab’)2 se produjeron originalmente como parejas de fragmentos de Fab’ que tienen cisteínas bisagras entre ellos. También se conocen otros acoplamientos químicos de fragmentos de anticuerpos. [0078] The Fab fragment contains the variable domains of heavy chain and light chain and also contains the constant domain of the light chain and the first constant domain (CH1) of the heavy chain. Fab ’fragments differ from Fab fragments by the addition of a series of residues at the carboxy terminal end of the CH1 domain of the heavy chain that include one or more cysteines of the hinge region of the antibody. Fab’-SH is the designation in the present invention for Fab ’in which the cysteine residue or residues of the constant domains transport a free thiol group. F (ab ’) 2 antibody fragments were originally produced as pairs of Fab’ fragments that have hinge cysteines between them. Other chemical couplings of antibody fragments are also known.

[0079] Los fragmentos de anticuerpo “Fv de cadena única” o “sFv” comprenden los dominios VH y VL del anticuerpo, en los que estos dominios se presentan en una única cadena de polipéptido. Generalmente, el polipéptido scFv comprende además un polipéptido enlazador entre los dominios VH y VL que permite que el sFv forme la estructura deseada para la unión a antígeno. Para una revisión de sFv véase Pluckthun en The Pharmacology of Monoclonal Antibodies, vol. 113, Rosenburg y Moore eds., Springer-Verlag, Nueva York, páginas 269-315 (1994). [0079] "Fv single chain" or "sFv" antibody fragments comprise the VH and VL domains of the antibody, in which these domains are presented in a single polypeptide chain. Generally, the scFv polypeptide further comprises a linker polypeptide between the VH and VL domains that allows the sFv to form the desired structure for antigen binding. For a review of sFv see Pluckthun in The Pharmacology of Monoclonal Antibodies, vol. 113, Rosenburg and Moore eds., Springer-Verlag, New York, pages 269-315 (1994).

[0080] El término “diabodies” se refiere a pequeños fragmentos de anticuerpos con dos sitios de unión a antígeno, cuyos fragmentos comprenden un dominio variable de cadena pesada (VH) conectado a un dominio variable de cadena ligera (VL) en la misma cadena de polipéptido (VH – VL). Utilizando un enlazador que es demasiado corto para permitir el apareamiento entre los dos dominios en la misma cadena, los dominios son forzados a emparejarse con los dominios complementarios de otra cadena y crean dos sitios de unión a antígeno. Los diabodies se describen más detalladamente en, por ejemplo, EP 404.097; WO 93/11161; Hudson et al. (2003) Nat. Med. 9:129134; y Hollinger et. al., Proc. Natl. Acad. Sci. USA, 90: 6444-6448 (1993). También se describen triabodies y tetrabodies en Hudson et al. (2003) Nat. Med. 9:129-134. [0080] The term "diabodies" refers to small antibody fragments with two antigen binding sites, whose fragments comprise a heavy chain variable domain (VH) connected to a light chain variable domain (VL) in the same chain of polypeptide (VH-VL). Using a linker that is too short to allow pairing between the two domains in the same chain, the domains are forced to pair with the complementary domains of another chain and create two antigen binding sites. Diabodies are described in more detail in, for example, EP 404,097; WO 93/11161; Hudson et al. (2003) Nat. Med. 9: 129134; and Hollinger et. al., Proc. Natl Acad. Sci. USA, 90: 6444-6448 (1993). Triabodies and tetrabodies are also described in Hudson et al. (2003) Nat. Med. 9: 129-134.

[0081] El término “anticuerpo monoclonal”, tal como se utiliza aquí, se refiere a un anticuerpo obtenido de una población de anticuerpos sustancialmente homogéneos, es decir, los anticuerpos individuales que componen la población son idénticos excepto por posibles mutaciones, por ejemplo, mutaciones naturales, que pueden presentarse en cantidades menores. Por tanto, el modificador "monoclonal” indica el carácter del anticuerpo como que no es una mezcla de anticuerpos discretos. En ciertas realizaciones, dicho anticuerpo monoclonal incluye habitualmente un anticuerpo que comprende una secuencia polipeptídica que se une a una diana, donde la secuencia polipeptídica de unión a la diana se obtuvo mediante un proceso que incluye la selección de una única secuencia polipeptídica de unión a la diana a partir de diversas secuencias polipeptídicas. Por ejemplo, el proceso de selección puede ser la selección de un único clon a partir de diversos clones, como un grupo de clones de hibridomas, clones de fagos o clones de ADN recombinante. Debería entenderse que una secuencia de unión a la diana seleccionada puede además alterarse, por ejemplo, para mejorar la afinidad por la diana, para humanizar la secuencia de unión a la diana, para mejorar su producción en el cultivo celular, para reducir su inmunogenicidad in vivo, para crear un anticuerpo multiespecífico, etc., y que un anticuerpo que comprende la secuencia de unión a la diana alterada es también un anticuerpo monoclonal de esta invención. A diferencia de las preparaciones de anticuerpos policlonales, que habitualmente incluyen diferentes anticuerpos dirigidos contra diferentes determinantes (epítopos), cada anticuerpo monoclonal de una preparación de anticuerpos monoclonales se dirige hacia un único determinante en un antígeno. Además de su especificidad, las preparaciones de anticuerpos monoclonales tienen la ventaja de que habitualmente no están contaminados por otras inmunoglobulinas. [0081] The term "monoclonal antibody", as used herein, refers to an antibody obtained from a population of substantially homogeneous antibodies, that is, the individual antibodies that make up the population are identical except for possible mutations, for example, natural mutations, which can occur in smaller amounts. Therefore, the "monoclonal" modifier indicates the character of the antibody as not being a mixture of discrete antibodies. In certain embodiments, said monoclonal antibody usually includes an antibody comprising a polypeptide sequence that binds to a target, where the target binding polypeptide sequence was obtained by a process that includes the selection of a single polypeptide binding sequence to the target. target from various polypeptide sequences. For example, the selection process may be the selection of a single clone from various clones, such as a group of hybridoma clones, phage clones or recombinant DNA clones. It should be understood that a selected target binding sequence can also be altered, for example, to improve target affinity, to humanize the target binding sequence, to improve its production in cell culture, to reduce its immunogenicity in alive, to create a multispecific antibody, etc., and that an antibody comprising the altered target binding sequence is also a monoclonal antibody of this invention. Unlike polyclonal antibody preparations, which usually include different antibodies directed against different determinants (epitopes), each monoclonal antibody of a monoclonal antibody preparation is directed towards a single determinant in an antigen. In addition to their specificity, monoclonal antibody preparations have the advantage that they are usually not contaminated by other immunoglobulins.

[0082] El modificador “monoclonal” indica el carácter del anticuerpo por obtenerse a partir de una población sustancialmente homogénea de anticuerpos y no debe interpretarse como que la producción del anticuerpo requiera ningún procedimiento en particular. Por ejemplo, los anticuerpos monoclonales a utilizar según la presente invención pueden obtenerse mediante diversas técnicas incluyendo, por ejemplo, el procedimiento del hibridoma (por ejemplo, Kohler et al., Nature, 256: 495 (1975); Harlow et al., Antibodies: A Laboratory Manual, (Cold Spring Harbor Laboratory Press, 2ª edición, 1988); Hammerling, et al., en: Monoclonal Antibodies and T-Cell Hybridomas 563-681 (Elsevier, N.Y., 1981)), métodos de ADN recombinante (véase, por ejemplo, la patente de Estados Unidos Nº 4.816.567), tecnologías de expresión en fagos (véase, por ejemplo, Clackson et al., Nature, 352: 624-628 (1991); Marks et al., J. Mol. Biol. 222: 581-597 (1992); Sidhu et al., J. Mol. Biol. 338(2): 299-310 (2004); Lee et al., J. Mol. Biol. 340(5): 1073-1093 (2004); Fellouse, Proc. Natl. Acad. Sci. USA 101 (34): 12467-12472 (2004) y Lee et al., J. Immunol. Methods 284(1-2): 119-132(2004) y las tecnologías para la producción de anticuerpos humanos o similares a humanos en animales que tienen partes o todos los loci de la inmunoglobulina humana o genes que codifican secuencias de inmunoglobulina humana (véanse, por ejemplo, los documentos WO98/24893; WO96/34096; WO96/33735; WO91/10741; Jakobovits et al., Proc. Natl. Acad. Sci. USA 90: 2551 (1993); Jakobovits et al., Nature [0082] The "monoclonal" modifier indicates the character of the antibody to be obtained from a substantially homogeneous population of antibodies and should not be construed as that the production of the antibody requires any particular procedure. For example, the monoclonal antibodies to be used according to the present invention can be obtained by various techniques including, for example, the hybridoma method (for example, Kohler et al., Nature, 256: 495 (1975); Harlow et al., Antibodies : A Laboratory Manual, (Cold Spring Harbor Laboratory Press, 2nd edition, 1988); Hammerling, et al., In: Monoclonal Antibodies and T-Cell Hybridomas 563-681 (Elsevier, NY, 1981)), recombinant DNA methods ( see, for example, U.S. Patent No. 4,816,567), phage display technologies (see, for example, Clackson et al., Nature, 352: 624-628 (1991); Marks et al., J. Mol. Biol. 222: 581-597 (1992); Sidhu et al., J. Mol. Biol. 338 (2): 299-310 (2004); Lee et al., J. Mol. Biol. 340 (5 ): 1073-1093 (2004); Fellouse, Proc. Natl. Acad. Sci. USA 101 (34): 12467-12472 (2004) and Lee et al., J. Immunol. Methods 284 (1-2): 119 -132 (2004) and technologies for the production of human antibodies or similar ah in animals that have parts or all of the human immunoglobulin loci or genes encoding human immunoglobulin sequences (see, for example, WO98 / 24893; WO96 / 34096; WO96 / 33735; WO91 / 10741; Jakobovits et al., Proc. Natl Acad. Sci. USA 90: 2551 (1993); Jakobovits et al., Nature

362: 255-258 (1993); Bruggemann et al., Year in Immunol. 7:33 (1993); patentes de Estados Unidos Nº. 5.545.807; 5.545.806; 5.569.825; 5.625.126; 5.633.425 y 5.661.016; Marks et al., Bio. Technology 10: 779-783 (1992); Lonberg et al., Nature 368: 856-859 (1994); Morrison, Nature 368: 812-813 (1994); Fishwild et al., Nature Biotechnol. 14: 845851 (1996); Neuberger, Nature Biotechnol. 14: 826 (1996) y Lonberg y Huszar, Intern. Rev. Immunol. 13: 65-93 (1995). 362: 255-258 (1993); Bruggemann et al., Year in Immunol. 7:33 (1993); United States Patent No. 5,545,807; 5,545,806; 5,569,825; 5,625,126; 5,633,425 and 5,661,016; Marks et al., Bio. Technology 10: 779-783 (1992); Lonberg et al., Nature 368: 856-859 (1994); Morrison, Nature 368: 812-813 (1994); Fishwild et al., Nature Biotechnol. 14: 845851 (1996); Neuberger, Nature Biotechnol. 14: 826 (1996) and Lonberg and Huszar, Intern. Rev. Immunol. 13: 65-93 (1995).

[0083] Entre los anticuerpos monoclonales de la presente invención se incluyen específicamente anticuerpos “quiméricos” en los que una parte de la cadena pesada y/o ligera es idéntica con u homóloga a las secuencias correspondientes en anticuerpos derivados de una especie particular o que pertenecen a una clase o subclase de anticuerpo particular, mientras que el resto de cadena o cadenas es idéntico con u homólogo a las secuencias correspondientes en anticuerpos derivados de otras especies o que pertenecen a otra clase o subclase de anticuerpo, así como fragmentos de dichos anticuerpos, siempre y cuando muestren la actividad biológica deseada (Patente de Estados Unidos No. 4.816.567; y Morrison et al., Proc. Natl. Acad. Sci. USA, 81: 6851-6855 (1984)). [0083] Monoclonal antibodies of the present invention specifically include "chimeric" antibodies in which a part of the heavy and / or light chain is identical with or homologous to the corresponding sequences in antibodies derived from a particular species or belonging to a particular class or subclass of antibody, while the rest of the chain or chains is identical or homologous to the corresponding sequences in antibodies derived from other species or belonging to another class or subclass of antibody, as well as fragments of said antibodies, as long as they show the desired biological activity (U.S. Patent No. 4,816,567; and Morrison et al., Proc. Natl. Acad. Sci. USA, 81: 6851-6855 (1984)).

[0084] Las formas “humanizadas” de anticuerpos no humanos (por ejemplo, murinos) son anticuerpos quiméricos que contienen una secuencia mínima derivada de inmunoglobulina no humana. En una realización, un anticuerpo humanizado es una inmunoglobulina humana (anticuerpo receptor) en que los residuos de una región hipervariable del receptor se sustituyen por residuos de una región hipervariable de una especie no humana (anticuerpo dador), tal como ratón, rata, conejo o primate no humano que tienen la especificidad, afinidad y/o capacidad deseadas. En algunos casos, los residuos de la estructura (“framework”) (FR) de la inmunoglobulina humana se sustituyen por los correspondientes residuos no humanos. Además, los anticuerpos humanizados pueden comprender residuos que no se encuentran ni en el anticuerpo receptor ni en el anticuerpo dador. Estas modificaciones se pueden realizar para refinar adicionalmente la acción del anticuerpo. En general, el anticuerpo humanizado comprenderá sustancialmente todos de por lo menos uno, y habitualmente dos, dominios variables, en que todos o sustancialmente todos los bucles hipervariables corresponden a aquellos de una inmunoglobulina no humana y todas o sustancialmente todas las regiones FR son aquellas de una secuencia de inmunoglobulina humana. El anticuerpo humanizado también comprenderá opcionalmente por lo menos una parte de una región constante (Fc) de inmunoglobulina, habitualmente la de una inmunoglobulina humana. Para más detalles, véase Jones et al., Nature, 321: 522-525 (1986), Reichmann et al., Nature 332: 323-329 (1988); y Presta, Curr. Op. Struct. Biol., 2: 593-596 (1992). Véanse también los siguientes artículos de revisión y referencias citadas en los mismos: Vaswani and Hamilton, Ann. Allergy, Asthma & Immunol. 1:105-115 (1998); Harris, Biochem. Soc. Transactions 23:1035-1038 (1995); Hurle and Gross, Curr. Op. Biotech. 5:428-433 (1994). [0084] "Humanized" forms of non-human antibodies (eg, murine) are chimeric antibodies that contain a minimal sequence derived from non-human immunoglobulin. In one embodiment, a humanized antibody is a human immunoglobulin (receptor antibody) in which the residues of a hypervariable region of the receptor are replaced by residues of a hypervariable region of a non-human species (donor antibody), such as mouse, rat, rabbit or non-human primate that have the desired specificity, affinity and / or capacity. In some cases, the structure residues ("framework") (FR) of the human immunoglobulin are replaced by the corresponding non-human residues. In addition, humanized antibodies may comprise residues that are neither found in the recipient antibody nor in the donor antibody. These modifications can be made to further refine the action of the antibody. In general, the humanized antibody will comprise substantially all of at least one, and usually two, variable domains, in which all or substantially all of the hypervariable loops correspond to those of a non-human immunoglobulin and all or substantially all of the FR regions are those of a sequence of human immunoglobulin. The humanized antibody will also optionally comprise at least a portion of a constant region (Fc) of immunoglobulin, usually that of a human immunoglobulin. For more details, see Jones et al., Nature, 321: 522-525 (1986), Reichmann et al., Nature 332: 323-329 (1988); and Presta, Curr. Op. Struct. Biol., 2: 593-596 (1992). See also the following review articles and references cited therein: Vaswani and Hamilton, Ann. Allergy, Asthma & Immunol 1: 105-115 (1998); Harris, Biochem. Soc. Transactions 23: 1035-1038 (1995); Hurle and Gross, Curr. Op. Biotech. 5: 428-433 (1994).

[0085] Un “anticuerpo humano” es aquel que comprende una secuencia de aminoácidos que corresponde a la de un anticuerpo producido por un humano y/o se ha producido utilizando cualquiera de las técnicas para fabricar anticuerpos humanos tal como se describe aquí. Dichas técnicas incluyen cribado de bibliotecas de combinación derivadas de humano, tales como bibliotecas de expresión en fagos (véanse, por ejemplo, Marks et al., J. Mol. Biol., [0085] A "human antibody" is one that comprises an amino acid sequence corresponding to that of an antibody produced by a human and / or has been produced using any of the techniques for making human antibodies as described herein. Such techniques include screening of human-derived combination libraries, such as phage display libraries (see, for example, Marks et al., J. Mol. Biol.,

222: 581-597 (1991) y Hoogenboom et al., Nucl. Acids Res., 19: 4133-4137 (1991)); utilizando líneas celulares de mieloma humano o heteromieloma ratón-humano para la producción de anticuerpos monoclonales humanos (véanse, por ejemplo, Kozbor J. Immunol., 133: 3001 (1984); Brodeur et al., Monoclonal Antibody Production Techniques and Applications, pág. 51-63 (Marcel Dekker, Inc., New York, 1987); y Boemer et al., J. Immunol., 147: 86 (1991)); y la generación de anticuerpos monoclonales en animales transgénicos (por ejemplo, ratones) que son capaces de producir un repertorio completo de anticuerpos humanos en ausencia de la producción de inmunoglobulinas endógenas (véanse, por ejemplo, Jakobovits et al., Proc. Natl. Acad. Sci USA, 90: 2551 (1993); Jakobovits et al., Nature. 362: 255 (1993); Bruggermann et al., Year in Immunol., 7: 33 (1993)). Esta definición de un anticuerpo humano excluye específicamente un anticuerpo humanizado que comprende residuos de unión a antígeno de un animal no humano. 222: 581-597 (1991) and Hoogenboom et al., Nucl. Acids Res., 19: 4133-4137 (1991)); using human myeloma or mouse-human heteromyeloma cell lines for the production of human monoclonal antibodies (see, for example, Kozbor J. Immunol., 133: 3001 (1984); Brodeur et al., Monoclonal Antibody Production Techniques and Applications, p. 51-63 (Marcel Dekker, Inc., New York, 1987); and Boemer et al., J. Immunol., 147: 86 (1991)); and the generation of monoclonal antibodies in transgenic animals (eg, mice) that are capable of producing a complete repertoire of human antibodies in the absence of endogenous immunoglobulin production (see, for example, Jakobovits et al., Proc. Natl. Acad. Sci USA, 90: 2551 (1993); Jakobovits et al., Nature. 362: 255 (1993); Bruggermann et al., Year in Immunol., 7: 33 (1993)). This definition of a human antibody specifically excludes a humanized antibody comprising antigen-binding residues of a non-human animal.

[0086] Un anticuerpo “madurado para afinidad” es aquel con una o más alteraciones en una o más de CDR del mismo que dan lugar a una mejora en la afinidad del anticuerpo para el antígeno, en comparación con un anticuerpo parental que no posee esta alteración o alteraciones. En una realización, un anticuerpo madurado para afinidad tiene afinidades nanomolares o incluso picomolares para el antígeno diana. Los anticuerpos madurados para afinidad se producen mediante procedimientos conocidos en la técnica. Marks et al. Bio/Technology 10:779-783 (1992) describe la maduración para afinidad por mezcla aleatoria de los dominios de VH y VL. La mutagénesis aleatoria de los residuos de HVR y/o armazón se describe por: Barbas et al. Proc Nat. Acad. Sci, USA 91:3809-3813 (1994); Schier et al. Gene 169:147-155 (1995); Yelton et al. J. Immunol. 155:1994-2004 (1995); Jackson et al., J. Immunol. 154(’7):3310-9 (1995); y Hawkins et al, J. Mol. Biol. 226:889-896 (1992). [0086] An "affinity matured" antibody is one with one or more alterations in one or more CDRs thereof that results in an improvement in the affinity of the antibody to the antigen, compared to a parental antibody that does not possess this alteration or alterations. In one embodiment, an affinity matured antibody has nanomolar or even picomolar affinities for the target antigen. Affinity matured antibodies are produced by methods known in the art. Marks et al. Bio / Technology 10: 779-783 (1992) describes maturation for affinity by random mixing of the VH and VL domains. Random mutagenesis of HVR residues and / or framework is described by: Barbas et al. Proc Nat. Acad. Sci, USA 91: 3809-3813 (1994); Schier et al. Gene 169: 147-155 (1995); Yelton et al. J. Immunol. 155: 1994-2004 (1995); Jackson et al., J. Immunol. 154 (’7): 3310-9 (1995); and Hawkins et al, J. Mol. Biol. 226: 889-896 (1992).

[0087] Un "anticuerpo de bloqueo" o un "anticuerpo antagonista" es aquel que inhibe o reduce una actividad biológica del antígeno al que se une. Ciertos anticuerpos de bloqueo o anticuerpos antagonistas inhiben parcial o completamente la actividad biológica del antígeno. [0087] A "blocking antibody" or an "antagonist antibody" It is one that inhibits or reduces a biological activity of the antigen to which it binds. Certain blocking antibodies or antagonistic antibodies partially or completely inhibit the biological activity of the antigen.

[0088] Una “molécula pequeña” o “molécula orgánica pequeña” se define en la presente invención como una molécula orgánica que tiene un peso molecular inferior a aproximadamente 500 daltons. [0088] A "small molecule" or "small organic molecule" is defined in the present invention as an organic molecule having a molecular weight of less than about 500 daltons.

[0089] Un "oligopéptido de unión a PRO" o un "oligopéptido que se une a PRO" es un oligopéptido que es capaz de unirse a PRO con suficiente afinidad, de manera que el oligopéptido es útil como agente de diagnóstico y/o terapéutico en el reconocimiento de PRO. En ciertas realizaciones, el grado de unión de un oligopéptido de unión a PRO a una proteína no PRO no relacionada es inferior a aproximadamente el 10% de la unión del oligopéptido de unión a PRO medida, por ejemplo, mediante un ensayo de resonancia de plasmón superficial. En ciertas realizaciones, un oligopéptido de unión a PRO tiene una constante de disociación (Kd) de : 1 !M, : 100 nM, : 10 nM, : 1 nM, o : 0,1 nM. [0089] A "PRO binding oligopeptide" or an "oligopeptide that binds to PRO" it is an oligopeptide that is capable of binding PRO with sufficient affinity, so that the oligopeptide is useful as a diagnostic and / or therapeutic agent in the recognition of PRO. In certain embodiments, the degree of binding of a PRO binding oligopeptide to an unrelated non-PRO protein is less than about 10% of the binding of the PRO binding oligopeptide measured, for example, by a plasmon resonance assay. superficial. In certain embodiments, a PRO binding oligopeptide has a dissociation constant (Kd) of: 1 µM,: 100 nM,: 10 nM,: 1 nM, or: 0.1 nM.

[0090] Una "molécula orgánica de unión a PRO" o una "molécula orgánica que se une a PRO" es una molécula orgánica diferente de un oligopéptido o anticuerpo tal como se define aquí que es capaz de unirse a PRO con suficiente afinidad, de manera que el molécula orgánica es útil como agente de diagnóstico y/o terapéutico en el reconocimiento de PRO. En ciertas realizaciones, el grado de unión de una molécula orgánica de unión a PRO a una proteína no PRO no relacionada es inferior a aproximadamente el 10% de la unión del molécula orgánica de unión a PRO medida, por ejemplo, mediante un ensayo de resonancia de plasmón superficial. En ciertas realizaciones, una molécula orgánica de unión a PRO tiene una constante de disociación (Kd) de : 1 !M, : 100 nM, : 10 nM, : 1 nM, o : 0,1 nM. [0090] An "organic PRO binding molecule" or an "organic molecule that binds to PRO" it is an organic molecule different from an oligopeptide or antibody as defined herein that is capable of binding PRO with sufficient affinity, so that the organic molecule is useful as a diagnostic and / or therapeutic agent in the recognition of PRO. In certain embodiments, the degree of binding of an organic PRO-binding molecule to an unrelated non-PRO protein is less than about 10% of the binding of the organic PRO-binding molecule measured, for example, by a resonance assay. of superficial plasmon. In certain embodiments, an organic PRO binding molecule has a dissociation constant (Kd) of: 1 µM,: 100 nM,: 10 nM,: 1 nM, or: 0.1 nM.

[0091] La constante de disociación (kd) de cualquier molécula que se une a un polipéptido diana se puede medir convenientemente utilizando el ensayo de resonancia de plasmón superficial. Dichos ensayos pueden utilizar un BIAcore™-2000 o un BIAcore™-3000 (BIAcore, Inc., Piscataway, NJ) a 25oC con chips CM5 de polipéptido diana inmovilizado a ~10 unidades de respuesta (RU). Brevemente, se activan chips biosensores de dextrano carboximetilado (CM5, BIAcore Inc.) con clorhidrato de N-etil-N’-(3-dimetilaminopropil)-carbodiimida (EDC) y Nhidroxisuccinimida (NHS) según las instrucciones del proveedor. El polipéptido diana se diluye con acetato de sodio 10 mM, pH 4,8, en 5 !g/ml (~0,2 !M) antes de la inyección a una velocidad de flujo de 5 !l/minuto para conseguir aproximadamente 10 unidades de respuesta (RU) de proteína acoplada. Tras la inyección de polipéptido diana, se inyecta etanolamina 1 M para bloquear los grupos no reaccionados. Para mediciones cinéticas, se inyectaron diluciones en serie de dos veces de la molécula de unión (0,78 nM a 500 nM) en PBS con Tween 20 al 0,05% (PBST) a 25°C a una velocidad de flujo de aproximadamente 25 !l/min. Las velocidades de asociación (kon) y velocidades de disociación (koff) se calculan utilizando un modelo de unión simple de Langmuir uno a uno (BIAcore Evaluation Software versión 3.2) mediante el ajuste simultáneo de los sensogramas de asociación y disociación. La constante de disociación en equilibrio (Kd) se calculó como la proporción koff/kon. Véase, por ejemplo, Chen, Y., et al., (1999) J. Mol Biol 293:865-881. Si la velocidad “on” de un anticuerpo supera 106 M-1S-1 mediante el ensayo de resonancia de plasmón superficial anterior, entonces la velocidad “on” se puede determinar utilizando una técnica de “quenching” fluorescente que mide el incremento o descenso en la intensidad de emisión por fluorescencia (excitación = 295 nm; emisión = 340 nm, paso de banda 16 nm) a 25°C de un anticuerpo 20 nM (forma Fab) en PBS, pH 7,2, en presencia de concentraciones crecientes de antígeno medidas en un espectrómetro, tal como un espectrofotómetro equipado con flujo interrumpido (Aviv Instruments) o un espectrofotómetro 8000-series SLM-Aminco (ThermoSpectronic) con una cuveta de agitada. [0091] The dissociation constant (kd) of any molecule that binds to a target polypeptide can be conveniently measured using the surface plasmon resonance assay. Such assays may use a BIAcore ™ -2000 or a BIAcore ™ -3000 (BIAcore, Inc., Piscataway, NJ) at 25 ° C with CM5 chips of immobilized target polypeptide at ~ 10 response units (RU). Briefly, carboxymethylated dextran biosensor chips (CM5, BIAcore Inc.) are activated with N-ethyl-N ’- (3-dimethylaminopropyl) -carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) according to the supplier's instructions. The target polypeptide is diluted with 10 mM sodium acetate, pH 4.8, in 5 µg / ml (~ 0.2 µM) before injection at a flow rate of 5 µl / minute to achieve approximately 10 response units (RU) of coupled protein. After injection of the target polypeptide, 1 M ethanolamine is injected to block unreacted groups. For kinetic measurements, serial dilutions of the binding molecule (0.78 nM to 500 nM) were injected twice in PBS with 0.05% Tween 20 (PBST) at 25 ° C at a flow rate of approximately 25! L / min. Association speeds (kon) and dissociation rates (koff) are calculated using a single-to-one Langmuir union model (BIAcore Evaluation Software version 3.2) by simultaneously adjusting the association and dissociation sensograms. The equilibrium dissociation constant (Kd) was calculated as the koff / kon ratio. See, for example, Chen, Y., et al., (1999) J. Mol Biol 293: 865-881. If the "on" velocity of an antibody exceeds 106 M-1S-1 by the above surface plasmon resonance assay, then the "on" velocity can be determined using a fluorescent quenching technique that measures the increase or decrease in fluorescence emission intensity (excitation = 295 nm; emission = 340 nm, bandpass 16 nm) at 25 ° C of a 20 nM antibody (Fab form) in PBS, pH 7.2, in the presence of increasing concentrations of antigen measured in a spectrometer, such as a spectrophotometer equipped with interrupted flow (Aviv Instruments) or an 8000-series SLM-Aminco spectrophotometer (ThermoSpectronic) with a stirring cuvette.

[0092] Un “liposoma” es una vesícula pequeña compuesta de varios tipos de lípidos, fosfolípidos y/o tensoactivos que es útil para la liberación de un agente, por ejemplo, un fármaco a un mamífero. Los componentes del liposoma se disponen habitualmente en una formación de bicapa, similar a la disposición de lípidos de las membranas biológicas. [0092] A "liposome" is a small vesicle composed of several types of lipids, phospholipids and / or surfactants that is useful for the release of an agent, for example, a drug to a mammal. The components of the liposome are usually arranged in a bilayer formation, similar to the lipid arrangement of the biological membranes.

[0093] La palabra “marcador” cuando se utiliza en la presente invención se refiere a un compuesto o composición detectable. El “marcador” puede ser detectable por sí mismo (por ejemplo, marcadores radioisótopos o marcadores fluorescentes) o, en el caso de un marcador enzimático, puede catalizar la alteración química de un compuesto o composición sustrato que da lugar a un producto detectable. Los radionucleidos que pueden servir como marcadores detectables incluyen, por ejemplo, I-131, I-123, I-125, Y-90, Re-188, Re-186, At-211, Cu-67, Bi-212, y Pd-109. [0093] The word "marker" when used in the present invention refers to a detectable compound or composition. The "label" can be detectable by itself (eg, radioisotope markers or fluorescent markers) or, in the case of an enzymatic label, can catalyze the chemical alteration of a substrate compound or composition that results in a detectable product. Radionuclides that can serve as detectable markers include, for example, I-131, I-123, I-125, Y-90, Re-188, Re-186, At-211, Cu-67, Bi-212, and PD-109.

[0094] Una molécula biológica "aislada", tal como un ácido nucleico, polipéptido o anticuerpo, es aquel que se ha identificado y separado y/o recuperado de por lo menos un componente de su medio natural. [0094] A biological molecule "isolated", such as a nucleic acid, polypeptide or antibody, is one that has been identified and separated and / or recovered from at least one component of its natural environment.

II. DESCRIPCIÓN DE CIERTAS REALIZACIONES II. DESCRIPTION OF CERTAIN EMBODIMENTS

[0095] En la presente se proporcionan variaciones de nucleótidos y aminoácidos asociados con tumores. Estas variaciones proporcionan biomarcadores para el cáncer y/o predisponen o contribuyen a la tumorigénesis o inducción del tumor. Por consiguiente, las variaciones descritas aquí son útiles en una variedad de disposiciones, por ejemplo, en métodos y composiciones relacionados con el diagnóstico y terapia contra el cáncer. [0095] Variations of nucleotides and amino acids associated with tumors are provided herein. These variations provide biomarkers for cancer and / or predispose or contribute to tumorigenesis or tumor induction. Accordingly, the variations described herein are useful in a variety of arrangements, for example, in methods and compositions related to cancer diagnosis and therapy.

A. Variaciones A. Variations

[0096] Se identificaron variaciones en 100 genes de veinticinco muestras de tumor de pulmón humano diferentes (carcinoma de pulmón de células no pequeña). Estas variaciones se indican en las tablas mostradas en las figuras 1, 2 y 3. [0096] Variations in 100 genes of twenty-five different human lung tumor samples (non-small cell lung carcinoma) were identified. These variations are indicated in the tables shown in Figures 1, 2 and 3.

1. Variaciones identificadas por MRD 1. Variations identified by MRD

[0097] Se identificaron las variaciones mediante MRD, tal como se describe posteriormente en el ejemplo A. Las variaciones se indican en la figura 1. En la figura 1, la primera columna de la tabla (“VARIANTE ID”) indica los números de identificación asignados a cada variación. La segunda columna (“UNIQID”) proporciona un número de identificación adicional específico de gen. La tercera columna (“NOMBRE DEL GEN (Ensembl)”) indica los genes en los que tiene lugar la variación. Los nombres de los genes están de acuerdo con la nomenclatura Ensembl. (El proyecto Ensembl se describe en Hubbard et al. (2006) Nucleic Acids Res. Database issue:D1-D8.) La cuartacolumna ("DESCRIPCIÓN DEL GEN") proporciona una descripción breve a partir de Ensembl de cada gen identificado en la cuarta columna. La quinta columna (“CAMBIO DE NT”) indica los cambios de nucleótidos por sus posiciones cromosómicas. Por ejemplo, la designación "9:130790136:G/T" en la columna cinco de la primera fila indica que un cambio de nucleótido en el polinucleótido ABL1 tiene lugar en el nucleótido 130790136 del cromosoma 9, y el cambio de nucleótido es una sustitución de G en esa posición con T. En la figura 1, los cambios de nucleótidos son todas sustituciones de nucleótidos únicos. Todas las sustituciones de nucleótidos identificadas en la figura 1 tenían lugar en las regiones codificantes de los genes indicados y todas son mutaciones no sinónimas o mutaciones no codificantes. Adicionalmente, todas las sustituciones de nucleótidos identificadas en la figura 1 son mutaciones somáticas (es decir, mutaciones halladas sólo en la muestra de tumor y no en la muestra normal emparejada con el paciente) [0097] Variations were identified by MRD, as described later in Example A. Variations are indicated in Figure 1. In Figure 1, the first column of the table ("VARIANT ID") indicates the numbers of Identification assigned to each variation. The second column ("UNIQID") provides an additional gene specific identification number. The third column ("GEN NAME (Ensembl)") indicates the genes in which the variation takes place. The names of the genes are in accordance with the Ensembl nomenclature. (The Ensembl project is described in Hubbard et al. (2006) Nucleic Acids Res. Database issue: D1-D8.) The fourth column (" GEN DESCRIPTION ") provides a brief description from Ensembl of each gene identified in the Fourth column The fifth column ("NT CHANGE") indicates the nucleotide changes by their chromosomal positions. For example, the designation "9: 130790136: G / T" in column five of the first row it indicates that a nucleotide change in polynucleotide ABL1 takes place at nucleotide 130790136 of chromosome 9, and the change of nucleotide is a substitution of G at that position with T. In Figure 1, the Nucleotide changes are all unique nucleotide substitutions. All nucleotide substitutions identified in Figure 1 took place in the coding regions of the indicated genes and all are non-synonymous mutations or non-coding mutations. Additionally, all nucleotide substitutions identified in Figure 1 are somatic mutations (i.e., mutations found only in the tumor sample and not in the normal sample paired with the patient)

[0098] La sexta columna (“CAMBIO DE AA”) de la tabla de la figura1 indica los cambios de aminoácidos resultantes de las sustituciones de nucleótido indicados en la columna previa. Las posiciones de aminoácidos designadas en la columna 6 se refieren a las secuencias de aminoácidos de PRO proporcionas en la tabla 1 siguiente, que son traducciones de las correspondientes secuencias de ADNc de PRO, también proporcionadas en la tabla 1. Las secuencias de aminoácidos y ADNc proporcionadas en la tabla 1 son de la base de datos de Ensembl. Las posiciones de aminoácidos designadas en la columna 6 también se refieren a las correspondientes posiciones de aminoácidos de fragmentos o variantes de PRO, (por ejemplo, variantes alélicas o variantes de empalme), que se [0098] The sixth column ("CHANGE OF AA") in the table in Figure 1 indicates the amino acid changes resulting from the nucleotide substitutions indicated in the previous column. The amino acid positions designated in column 6 refer to the PRO amino acid sequences provided in Table 1 below, which are translations of the corresponding PRO cDNA sequences, also provided in Table 1. The amino acid and cDNA sequences provided in table 1 are from the Ensembl database. The amino acid positions designated in column 6 also refer to the corresponding amino acid positions of PRO fragments or variants, (eg allelic variants or splice variants), which are

pueden identificar de manera rutinaria utilizando las alineaciones de secuencia o técnicas similares. Cuando la sustitución de nucleótido daba lugar a un codón de parada (es decir, una mutación no codificante), el correspondiente cambio de aminoácido se indica en la columna 6 por una “O” (por ejemplo, véase la Variante ID 10015, que indica un cambio de aminoácido de "1170Q�OU). La septima columna ("DOMINIO") indica, para algunas 5 de las variaciones, los dominios de proteína en que tienen lugar los cambios de aminoácidos. Los dominios de proteína se indican mediante la nomenclatura Pfam (Véanse, por ejemplo, Bateman et al. (2004) Nucleic Acids Res. 32(1):D138-141.) They can routinely identify using sequence alignments or similar techniques. When nucleotide substitution resulted in a stop codon (ie a non-coding mutation), the corresponding amino acid change is indicated in column 6 by an "O" (for example, see Variant ID 10015, which indicates an amino acid change of " 1170Q�OU). The seventh column ("DOMAIN") indicates, for some 5 of the variations, the protein domains in which amino acid changes take place. Protein domains are indicated by the nomenclature Pfam (See, for example, Bateman et al. (2004) Nucleic Acids Res. 32 (1): D138-141.)

TABLA 1 10 TABLE 1 10

NOMBRE DEL GEN GEN NAME: SECUENCIA SEC ID NO. de ADNc SECUENCIA SEC ID NO. de AMINOÁCIDO SEQUENCE SEQ ID NO. cDNA SEQUENCE SEQ ID NO. of AMINO ACID

ABL1 ABL1: 1 38 one 38

APC APC: 2 39 2 39

ATMATM: 3 40 3 40

ATRATR: 4 41 4 41

FBXW7 FBXW7: 5 42 5 42

FLT1FLT1: 6 43 6 43

FLT3FLT3: 7 44 7 44

FRAP FRAP: 8 45 8 Four. Five

KDR KDR: 9 46 9 46

METMET: 10 47 10 47

MLLMLL: 11 48 eleven 48

NF1 NF1: 12 49 12 49

PDGFRA PDGFRA: 13 50 13 fifty

PDGFRB PDGFRB: 14 51 14 51

PLK1 PLK1: 15 52 fifteen 52

TCF1TCF1: 16 53 16 53

TP53 TP53: 17 54 17 54

TSHRTSHR: 18 55 18 55

[0099] La figura 2 indica las variaciones somáticas de nucleótidos que se encuentran en las regiones de los sitios de empalme de consenso de seis genes. En la figura 2, la primera columna de la tabla (“VARIANTE ID") indica los números de identificación asignados a cada variación. La segunda columna ("UNQID") proporciona un número de 15 identificación adicional específico de gen. La tercera columna (“GEN”) indica los genes en que tiene lugar las variaciones. Los nombres de los genes son de acuerdo con la nomenclatura Ensembl. La cuarta columna (“DESCRIPCIÓN DEL GEN”) proporciona una descripción breve de Ensembl de cada gen identificado en la cuarta columna. La quinta columna (“CAMBIO De NT”) se refiere a cambios de nucleótidos que se identificaron mediante MRD. La sexta columna (“FRECUENCIA”) indica el número de veces que se encontró una variación particular. La 20 séptima columna ("EXÓN AFECTADO") se refiere a los exones asociados con las variaciones del sitio de empalme de consenso. La octava columna (“SITIO DE EMPALME”) describe con particularidad donde tuvieron lugar lasvariaciones en los sitios de empalme de consenso. La novena columna (“EFECTO DE PROTEÍNA”) indica si las variaciones dieron lugar a una proteína dentro del marco o fuera del marco. La décima columna (“DOMINIO”) indica los dominios de proteína afectados por dos de las variaciones. La última columna (“ESTADO DEL SALTO”) indica si [0099] Figure 2 indicates the somatic nucleotide variations found in the regions of the six gene consensus splice sites. In Figure 2, the first column of the table ("VARIATION ID" indicates the identification numbers assigned to each variation. The second column ("UNQID") provides a number of 15 additional gene specific identification. The third column ("GEN") indicates the genes in which the variations take place. The names of the genes are according to the Ensembl nomenclature. The fourth column ("GEN DESCRIPTION") provides a brief Ensembl description of each gene identified in the fourth column. The fifth column ("NT CHANGE") refers to nucleotide changes that were identified by MRD. The sixth column ("FREQUENCY") indicates the number of times a particular variation was found. The seventh column ("EXON AFFECTED") refers to the exons associated with variations in the consensus splice site. The eighth column ("SOCKET SITE") describes in particular where the variations in the consensus splicing sites took place. The ninth column ("PROTEIN EFFECT") indicates whether the variations resulted in a protein within or outside the frame. The tenth column ("DOMAIN") indicates the protein domains affected by two of the variations. The last column (“JUMP STATUS”) indicates if

25 los exones asociados con las variaciones del sitio de empalme de consenso se saltaron o no durante el empalme de ARNm. Las secuencias de aminoácidos codificadas por ciertos genes indicados en la figura 2 se proporcionan en la tabla 2: 25 exons associated with variations in the consensus splice site were skipped or not during mRNA splicing. The amino acid sequences encoded by certain genes indicated in Figure 2 are provided in Table 2:

TABLA 2 30 TABLE 2 30

NOMBRE DEL GEN GEN NAME: SECUENCIA SEC ID NO. de AMINOÁCIDO SEQUENCE SEQ ID NO. of AMINO ACID

ERBB4 ERBB4: 75 75

FGFR2 FGFR2: 76 76

MAP4K4 MAP4K4: 77 77

PDK1 PDK1: 78 78

RB1RB1: 79 79

2. Variaciones identificadas mediante secuenciación Sanger 2. Variations identified by Sanger sequencing

[0100] Se identificaron variaciones mediante secuenciación Sanger, tal como se describe posteriormente en el 35 ejemplo B. Las variaciones se indican en la figura 3. La primera columna de la tabla ("VARIANTE ID") indica los números de identificación asignados a cada variación. La segunda columna ("UNQID") indica los números de identificación adicionales específicos de genes. La tercera columna ("NOMBRE DEL GEN (HUGO)") indica los genes en que tienen lugar las variaciones. Los nombres de los genes están de acuerdo con la nomenclatura de la [0100] Variations were identified by Sanger sequencing, as described later in Example B. Variations are indicated in Figure 3. The first column of the table ("VARIABLE ID") indicates the identification numbers assigned to Each variation The second column ("UNQID") indicates the additional identification numbers specific to genes. The third column ("GEN NAME (HUGO)") indicates the genes in which the variations take place. The names of the genes are in accordance with the nomenclature of the

Organización del Genoma Humano (HUGO). Véase Wain et al. (2002) Genomics 79:464-470. La cuarta columna (“DESCRIPCIÓN DEL GEN”) proporciona una breve descripción de HUGO de cada gen identificado en la tercera columna. La quinta columna ("CAMBIO DE NT”) indica el cambio de nucleótido en cada gen. En este estudio, los cambios de nucleótidos fueron todas sustituciones de un solo nucleótido. El término "HETSUB" en la quinta columna 5 representa “sustitución heterozigótica”, lo que significa que tanto la variación indicada como el alelo de tipo salvaje se detectaron en la muestra de tumor. El término "HOMSUB" representa "sustitución homozigótica," lo que significa que la variación indicada se detectó en la muestra de tumor y el alelo de tipo salvaje no se detectó en la muestra del tumor. Esto puede tener lugar, por ejemplo, si el tumor ha experimentado una pérdida de heterozigosidad (por ejemplo, donde una copia de un gen determinado contiene una variación, y la otra copia contiene una deleción en el 10 correspondiente gen). Los números de nucleótidos se refieren a posiciones de nucleótidos en las secuencias de ADNc que corresponden a los genes indicados. Por ejemplo, la variante ID 912 es una sustitución heterozigótica designada "2667A>G," los que indica que una “A” ha sido sustituida por una “G” en una copia del gen PTCH, teniendo lugar la sustitución en una posición genómica correspondiente la nucleótido 2667 de la secuencia de ADNc (SEC ID NO:32) del gen PTCH. Para cada gen indicado en la figura 3, las secuencias de ADNc correspondientes y 15 sus traducciones se proporciona en el listado de secuencias, tal como se indica en la tabal 3 siguiente. Human Genome Organization (HUGO). See Wain et al. (2002) Genomics 79: 464-470. The fourth column ("GEN DESCRIPTION") provides a brief description of HUGO of each gene identified in the third column. The fifth column ("NT CHANGE") indicates the change of nucleotide in each gene. In this study, the nucleotide changes were all substitutions of a single nucleotide. The term " HETSUB " in the fifth column 5 represents "heterozygous substitution", which means that both the indicated variation and the wild-type allele were detected in the tumor sample. The term " HOMSUB " represents " homozygous substitution, " which means that the indicated variation was detected in the tumor sample and the wild-type allele was not detected in the tumor sample. This can take place, for example, if the tumor has experienced a loss of heterozygosity (for example, where one copy of a given gene contains a variation, and the other copy contains a deletion in the corresponding gene). Nucleotide numbers refer to nucleotide positions in the cDNA sequences that correspond to the indicated genes. For example, variant ID 912 is a heterozygous substitution designated " 2667A> G, " which indicates that an "A" has been replaced by a "G" in a copy of the PTCH gene, substitution taking place at a corresponding genomic position nucleotide 2667 of the cDNA sequence (SEQ ID NO: 32) of the PTCH gene . For each gene indicated in Figure 3, the corresponding cDNA sequences and their translations are provided in the sequence listing, as indicated in table 3 below.

TABLA 3 TABLE 3

AKT2 AKT2: 19 56 19 56

AURKC AURKC: 20 57 twenty 57

BCL2L1 BCL2L1: 21 58 twenty-one 58

CDKN2A CDKN2A: 22 59 22 59

ERBB3 ERBB3: 23 60 2. 3 60

ERBB4 ERBB4: 24 61 24 61

FGFR3 FGFR3: 25 62 25 62

FRAP1 FRAP1: 26 63 26 63

KDR KDR: 27 64 27 64

MAP2K2 MAP2K2: 28 65 28 65

MET MET: 29 66 29 66

PIK3CA PIK3CA: 30 67 30 67

PLK1 PLK1: 31 68 31 68

PTCHPTCH: 32 69 32 69

RB1 RB1: 33 70 33 70

RET RET: 34 71 3. 4 71

STK6STK6: 35 72 35 72

TGFBR2 TGFBR2: 36 73 36 73

TP53 TP53: 37 74 37 74

20 Todas las sustituciones de nucleótidos identificados en la figura 3 tuvieron lugar en las regiones codificantes de los genes indicados. Adicionalmente, todas las sustituciones de nucleótidos identificadas en este estudio se validaron (es decir, se confirmaron) mediante la resecuenciación del ADN de la muestra o muestras de tumor en que se descubrió inicialmente la variación. 20 All nucleotide substitutions identified in Figure 3 took place in the coding regions of the indicated genes. Additionally, all nucleotide substitutions identified in this study were validated (i.e. confirmed) by resequencing the DNA of the sample or tumor samples in which the variation was initially discovered.

25 [0101] La sexta columna (“CAMBIO DE AA”) de la tabla en la figura 3 indica los cambios de aminoácidos resultantes de las sustituciones de nucleótidos indicados en la columna anterior, Los aminoácidos se numeran según sus posiciones en las secuencias de ADNc traducidas. Cuando una sustitución de nucleótido daba lugar a un codón de parada (es decir, una mutación no codificante), el correspondiente cambio de aminoácido se indica por una “O” (por ejemplo, véase la Variante ID 4356, que indica un cambio de aminoácido de "61C>O"). La séptima columna 30 (“EFECTO”) indica si la variación da lugar a una sustitución de aminoácido no sinónima (“No sin.”) o en una mutación no codificante (“no codificante”). La octava columna (“DOMINIO”) indica, para algunas de las variaciones, los dominios de proteína en que tienen lugar los cambios de aminoácidos. Los dominios de proteínas se indican mediante la nomenclatura Pfam. (Véase, por ejemplo, Bateman et al. (2004) Nucleic Acids Res. 32(1):D138-141.) [0101] The sixth column ("CHANGE OF AA") in the table in Figure 3 indicates the amino acid changes resulting from the nucleotide substitutions indicated in the previous column. Amino acids are numbered according to their positions in the cDNA sequences. translated. When a nucleotide substitution resulted in a stop codon (ie, a non-coding mutation), the corresponding amino acid change is indicated by an "O" (for example, see Variant ID 4356, which indicates an amino acid change of " 61C> O "). Seventh column 30 ("EFFECT") indicates whether the variation results in a non-synonymous amino acid substitution ("Not without.") Or in a non-coding ("non-coding") mutation. The eighth column ("DOMAIN") indicates, for some of the variations, the protein domains in which amino acid changes take place. Protein domains are indicated by the Pfam nomenclature. (See, for example, Bateman et al. (2004) Nucleic Acids Res. 32 (1): D138-141.)

35 [0102] La novena columna (“SOMÁTICA O LÍNEA GERMIANL”) indica si una variación determinada se halló sólo en la muestra del tumor y no en la muestra normal emparejada con el paciente (es decir, una mutación somática), o si se halló tanto en la muestra de tumor como en la muestra normal emparejada con el paciente (Es decir, un polimorfismo en la línea germinal). Se hallaron ciertas variaciones en múltiples muestras de tumor. En dichos casos, se clasificó una variación como una mutación somática si se halló que estaba ausente de por lo menos una muestra 40 normal emparejada con el paciente. Así mismo, una variación se clasificó como un polimorfismo en la línea germinal si se halló que estaba presente en por lo menos una muestra normal emparejada con el paciente. 35 [0102] The ninth column ("SOMATIC OR GERMIANL LINE") indicates whether a given variation was found only in the tumor sample and not in the normal sample paired with the patient (ie, a somatic mutation), or if found both in the tumor sample and in the normal sample paired with the patient (that is, a germline polymorphism). Certain variations were found in multiple tumor samples. In these cases, a variation was classified as a somatic mutation if it was found to be absent from at least one normal sample paired with the patient. Likewise, a variation was classified as a germline polymorphism if it was found that it was present in at least one normal sample paired with the patient.

3. Tipos de tumores y familias de proteínas 3. Types of tumors and protein families

[0103] Las variaciones indicadas en las figuras 1, 2 y 3 se identificaron en carcinomas de pulmón de célula no pequeña. Se puede utilizar el cribado de rutina para determinar si las variaciones tienen lugar en otros tipos de cánceres. Las composiciones y métodos de la presente invención son aplicables a cualquier cáncer que comprende variaciones en los genes indicados y/o los polipéptidos codificados. [0103] The variations indicated in Figures 1, 2 and 3 were identified in non-small cell lung carcinomas. Routine screening can be used to determine if variations occur in other types of cancers. The compositions and methods of the present invention are applicable to any cancer comprising variations in the indicated genes and / or the encoded polypeptides.

[0104] Se hallaron variaciones en genes que codifican proteínas de una variedad de familias de proteínas. Por ejemplo, se hallaron variaciones en un conjunto de genes que codifican quinasas, incluyendo receptores tirosina quinasas (RTKs). Generalmente, la activación de quinasas está asociada a menudo con la proliferación celular y la inducción de tumores. De este modo, las variaciones en genes que codifican quinasas pueden ser mutaciones de “ganar una función” que incrementan la actividad de quinasa. Los tumores en que se detectan dichas variaciones pueden ser por tanto sensibles a antagonistas de quinasa. En la técnica se conocen actualmente un conjunto de antagonistas de quinasa. Dichos antagonistas de quinasa incluyen, pero sin limitación, anticuerpos antagonistas y antagonistas de molécula pequeña, por ejemplo, 3-[2,4-dimetilpirrol-5-il)metiliden]-indolin-2-ona ("SU5416"); imatinib (Gleevec®), una 2-fenilaminopirimidina; 1-tert-butil-3-[6-(3,5-dimetoxi-fenil)-2-(4-dietilamino-butilamino)-pirido[2,3d]pirimidin-7-il]-urea ("PD173074") (véase, por ejemplo, Moffa et al. (2004) Mol. Cancer. Res. 2:643-652); y indolinonas, tales como 3-[3-(2-carboxietil)-4-metilpyrrol-2-metilidenil]-2-indolinona ("SU5402") (véase, por ejemplo, Bernard-Pierrot (2004) Oncogene 23:9201-9211). Un antagonista de quinasa también puede ser un inhibidor de EGFR o un inhibidor de tirosina quinasa, tal como se definen aquí. [0104] Variations were found in genes encoding proteins from a variety of protein families. For example, variations were found in a set of genes that encode kinases, including tyrosine kinase receptors (RTKs). Generally, kinase activation is often associated with cell proliferation and tumor induction. Thus, variations in genes encoding kinases can be "win a function" mutations that increase kinase activity. Tumors in which such variations are detected may therefore be sensitive to kinase antagonists. A set of kinase antagonists are currently known in the art. Such kinase antagonists include, but are not limited to, small molecule antagonist and antagonist antibodies, for example, 3- [2,4-dimethylpyrrol-5-yl) methylidene] -indolin-2-one (" SU5416 "); imatinib (Gleevec®), a 2-phenylaminopyrimidine; 1-tert-butyl-3- [6- (3,5-dimethoxy-phenyl) -2- (4-diethylamino-butylamino) -pyrido [2,3d] pyrimidin-7-yl] -urea (" PD173074 " ) (see, for example, Moffa et al. (2004) Mol. Cancer. Res. 2: 643-652); and indolinones, such as 3- [3- (2-carboxyethyl) -4-methylpyrrol-2-methylidenyl] -2-indolinone (" SU5402 ") (see, for example, Bernard-Pierrot (2004) Oncogene 23: 9201 -9211). A kinase antagonist can also be an EGFR inhibitor or a tyrosine kinase inhibitor, as defined herein.

[0105] También se hallaron variaciones en los genes supresores de tumores (por ejemplo, p53 y retinoblastoma). En general, la pérdida de función del supresor de tumor está a menudo asociada con la proliferación celular y la inducción de tumores. De este modo, las variaciones en genes que codifican supresores de tumores pueden ser mutaciones de “pérdida de función” completa o parcial que disminuyen la función supresora del tumor. Los tumores en que se detectan dichas variaciones pueden ser sensibles a agonistas supresores de tumores. Un agonista supresor de tumor puede ser, por ejemplo, un anticuerpo agonista, un polinucleótido que codifica un supresor de tumor, el propio supresor de tumor, o una fusión supresor de tumor-Fc. [0105] Variations were also found in tumor suppressor genes (for example, p53 and retinoblastoma). In general, loss of tumor suppressor function is often associated with cell proliferation and tumor induction. Thus, variations in genes encoding tumor suppressors can be complete or partial "loss of function" mutations that decrease tumor suppressor function. Tumors in which such variations are detected may be sensitive to tumor suppressor agonists. A tumor suppressor agonist can be, for example, an agonist antibody, a polynucleotide encoding a tumor suppressor, the tumor suppressor itself, or a tumor suppressor-Fc fusion.

B. Composiciones B. Compositions

[0106] En un aspecto, se proporciona un polinucleótido aislado que comprende por lo menos un fragmento de un polinucleótido de PRO, donde el fragmento comprende una variación de nucleótido. En una realización, la variación de nucleótido es en una posición de nucleótido seleccionada de las figuras 1-3. En una de dichas realizaciones, la variación de nucleótido es un cambio de nucleótido seleccionado de las figuras 1-3. En otra realización, un fragmento de un polinucleótido de PRO tiene por lo menos aproximadamente 10 nucleótidos de longitud, alternativamente por lo menos aproximadamente 15 nucleótidos de longitud, alternativamente por lo menos aproximadamente 20 nucleótidos de longitud, alternativamente por lo menos aproximadamente 30 nucleótidos de longitud, alternativamente por lo menos aproximadamente 40 nucleótidos de longitud, alternativamente por lo menos aproximadamente 50 nucleótidos de longitud, alternativamente por lo menos aproximadamente 60 nucleótidos de longitud, alternativamente por lo menos aproximadamente 70 nucleótidos de longitud, alternativamente por lo menos aproximadamente 80 nucleótidos de longitud, alternativamente por lo menos aproximadamente 90 nucleótidos de longitud, alternativamente por lo menos aproximadamente 100 nucleótidos de longitud, alternativamente por lo menos aproximadamente 110 nucleótidos de longitud, alternativamente por lo menos aproximadamente 120 nucleótidos de longitud, alternativamente por lo menos aproximadamente 130 nucleótidos de longitud, alternativamente por lo menos aproximadamente 140 nucleótidos de longitud, alternativamente por lo menos aproximadamente 150 nucleótidos de longitud, alternativamente por lo menos aproximadamente 160 nucleótidos de longitud, alternativamente por lo menos aproximadamente 170 nucleótidos de longitud, alternativamente por lo menos aproximadamente 180 nucleótidos de longitud, alternativamente por lo menos aproximadamente 190 nucleótidos de longitud, alternativamente por lo menos aproximadamente 200 nucleótidos de longitud, alternativamente por lo menos aproximadamente 250 nucleótidos de longitud, alternativamente por lo menos aproximadamente 300 nucleótidos de longitud, alternativamente por lo menos aproximadamente 350 nucleótidos de longitud, alternativamente por lo menos aproximadamente 400 nucleótidos de longitud, alternativamente por lo menos aproximadamente 450 nucleótidos de longitud, alternativamente por lo menos aproximadamente 500 nucleótidos de longitud, alternativamente por lo menos aproximadamente 600 nucleótidos de longitud, alternativamente por lo menos aproximadamente 700 nucleótidos de longitud, alternativamente por lo menos aproximadamente 800 nucleótidos de longitud, alternativamente por lo menos aproximadamente 900 nucleótidos de longitud, alternativamente por lo menos aproximadamente 1000 nucleótidos de longitud, y alternativamente aproximadamente la longitud de la secuencia codificante de longitud completa. En este contexto, el término "aproximadamente" significa la longitud de secuencia de nucleótidos de referencia más o menos un 10% de la longitud referenciada. En otra realización, el polinucleótido comprende una variación de nucleótido en una secuencia de polinucleótido seleccionada de SEC ID NO: 1-37 o un fragmento de la misma. En otra realización, se proporciona el complemento de cualquiera de los polinucleótidos anteriores. En otra realización, se proporciona un PRO codificado por cualquiera de los polinucleótidos anteriores. [0106] In one aspect, an isolated polynucleotide is provided comprising at least one fragment of a PRO polynucleotide, wherein the fragment comprises a nucleotide variation. In one embodiment, the nucleotide variation is in a nucleotide position selected from Figures 1-3. In one such embodiment, the nucleotide variation is a nucleotide change selected from Figures 1-3. In another embodiment, a fragment of a PRO polynucleotide is at least about 10 nucleotides in length, alternatively at least about 15 nucleotides in length, alternately at least about 20 nucleotides in length, alternately at least about 30 nucleotides in length , alternatively at least about 40 nucleotides in length, alternately at least about 50 nucleotides in length, alternately at least about 60 nucleotides in length, alternately at least about 70 nucleotides in length, alternately at least about 80 nucleotides in length , alternatively at least about 90 nucleotides in length, alternatively at least about 100 nucleotides in length, alternately at least about 110 nucleotides in length, alternately at least about 120 nucleotides in length, alternatively at least about 130 nucleotides in length, alternately at least about 140 nucleotides in length, alternately at least about 150 nucleotides in length, alternately at least about 160 nucleotides in length, alternately at least about 170 nucleotides in length, alternatively at least about 180 nucleotides in length, alternately at least about 190 nucleotides in length, alternately at least about 200 nucleotides in length, alternately at least about 250 nucleotides in length, alternately at least about 300 nucleotides in length, alternately at least about 350 nucleotides in length, alternately at least about 400 nucleotides in length, alternately at least about 450 nucleotides tidos in length, alternatively at least about 500 nucleotides in length, alternately at least about 600 nucleotides in length, alternately at least about 700 nucleotides in length, alternately at least about 800 nucleotides in length, alternately at least about 900 nucleotides in length, alternatively at least about 1000 nucleotides in length, and alternatively approximately the length of the full length coding sequence. In this context, the term " approximately " means the reference nucleotide sequence length plus or minus 10% of the referenced length. In another embodiment, the polynucleotide comprises a nucleotide variation in a polynucleotide sequence selected from SEQ ID NO: 1-37 or a fragment thereof. In another embodiment, the complement of any of the above polynucleotides is provided. In another embodiment, a PRO encoded by any of the above polynucleotides is provided.

[0107] En una realización, un polinucleótido aislado proporcionada aquí se marca de forma detectable, por ejemplo, con un radioisótopo, un agente fluorescente, o un agente cromogénico. En otra realización, un polinucleótido aislado es un cebador. En otra realización, un polinucleótido aislado es un oligonucleótido, por ejemplo, un oligonucleótido específico de alelo. En otra realización, un oligonucleótido puede tener, por ejemplo, 7-60 nucleótidos de longitud, 945 nucleótidos de longitud, 15-30 nucleótidos de longitud, o 18-25 nucleótidos de longitud. En otra realización, un oligonucleótido puede ser, por ejemplo, PNA, morfolino-fosforamidatos, LNA, o 2’-alcoxialcoxi. Los oligonucleótidos tal como se proporcionan aquí son útiles, por ejemplo, como sondas de hibridación para la detección de variaciones de nucleótidos. [0107] In one embodiment, an isolated polynucleotide provided herein is detectably labeled, for example, with a radioisotope, a fluorescent agent, or a chromogenic agent. In another embodiment, an isolated polynucleotide is a primer. In another embodiment, an isolated polynucleotide is an oligonucleotide, for example, an allele specific oligonucleotide. In another embodiment, an oligonucleotide can be, for example, 7-60 nucleotides in length, 945 nucleotides in length, 15-30 nucleotides in length, or 18-25 nucleotides in length. In another embodiment, an oligonucleotide can be, for example, PNA, morpholino phosphoramidates, LNA, or 2'-alkoxyalkoxy. Oligonucleotides as provided herein are useful, for example, as hybridization probes for the detection of nucleotide variations.

[0108] En otro aspecto, se proporciona un oligonucleótido específico de alelo que se hibrida a una región de un polinucleótido PRO que comprende una variación de nucleótido (por ejemplo, una sustitución). En una realización, la variación de nucleótido es en una posición de nucleótido seleccionada de las figuras 1-3. En una de dichas realizaciones, la variación de nucleótido es un cambio de nucleótido seleccionado de las figuras 1-3. El oligonucleótido específico de alelo, cuando se hibrida a la región del polinucleótido de PRO, comprende un nucleótido que cuando se hibrida a la región del polinucleótido de PRO, comprende un nucleótidos que se empareja en las bases con la variación de nucleótido. En otra realización, se proporciona el complemento de un oligonucleótido específico de alelo. En otra realización, un microarray comprende un oligonucleótido específico de alelo o su complemento. En otra realización, un oligonucleótido específico de alelo o su complemento es un cebador específico de alelo. [0108] In another aspect, an allele-specific oligonucleotide is provided that hybridizes to a region of a PRO polynucleotide comprising a nucleotide variation (eg, a substitution). In one embodiment, the nucleotide variation is in a nucleotide position selected from Figures 1-3. In one such embodiment, the nucleotide variation is a nucleotide change selected from Figures 1-3. The allele-specific oligonucleotide, when hybridized to the PRO polynucleotide region, comprises a nucleotide that when hybridized to the PRO polynucleotide region, comprises a nucleotide that pairs at the bases with the nucleotide variation. In another embodiment, the complement of an allele-specific oligonucleotide is provided. In another embodiment, a microarray comprises an allele-specific oligonucleotide or its complement. In another embodiment, an allele specific oligonucleotide or its complement is an allele specific primer.

[0109] Un oligonucleótido específico de alelo se puede utilizar conjuntamente con un oligonucleótido de control que es idéntico al oligonucleótido específico de alelo, a excepción de que el nucleótido que se empareja específicamente en las bases con la variación de nucleótido se sustituye por un nucleótido que se empareja específicamente en las bases con el correspondiente nucleótido presente en el polinucleótido de PRO de tipo salvaje. Dichos oligonucleótidos se pueden utilizar en ensayos de unión competitiva bajo condiciones de hibridación que permiten que los oligonucleótidos distingan entre un polinucleótido de PRO que comprende una variación de nucleótido y un polinucleótido de PRO que comprende el correspondiente nucleótido de tipo salvaje. Utilizando métodos de rutina basados, por ejemplo, en la longitud y composición de las bases de los oligonucleótidos, un experto en la materia puede llegar a condiciones de hibridación adecuadas bajo las cuales (a) un oligonucleótido específico de alelo se unirá preferiblemente a un polinucleótido de PRO que comprende una variación de nucleótido en relación a un polinucleótido de PRO de tipo salvaje, y (b) el oligonucleótido de control se unirá preferiblemente a un polinucleótido de PRO de tipo salvaje en relación con un polinucleótido de PRO que comprende una variación de nucleótido. Entre las condiciones de ejemplo se incluyen condiciones de astringencia elevada, por ejemplo, condiciones de hibridación de 5x EDTA con solución salina de fosfato estándar (SSPE) y NaDodSO4 (SDS) al 0,5% a 55°C, seguido de lavado con 2X SSPE y SDS al 0,1% a 55°C o temperatura ambiente. [0109] An allele-specific oligonucleotide may be used in conjunction with a control oligonucleotide that is identical to the allele-specific oligonucleotide, except that the nucleotide that specifically matches the bases with the nucleotide variation is replaced by a nucleotide that it is specifically paired in the bases with the corresponding nucleotide present in the wild-type PRO polynucleotide. Such oligonucleotides can be used in competitive binding assays under hybridization conditions that allow oligonucleotides to distinguish between a PRO polynucleotide comprising a nucleotide variation and a PRO polynucleotide comprising the corresponding wild type nucleotide. Using routine methods based, for example, on the length and composition of the oligonucleotide bases, a person skilled in the art can reach suitable hybridization conditions under which (a) an allele-specific oligonucleotide will preferably bind a polynucleotide of PRO comprising a nucleotide variation in relation to a wild-type PRO polynucleotide, and (b) the control oligonucleotide will preferably bind to a wild-type PRO polynucleotide in relation to a PRO polynucleotide comprising a variation of nucleotide Example conditions include high astringency conditions, for example, 5x EDTA hybridization conditions with standard phosphate saline solution (SSPE) and 0.5% NaDodSO4 (SDS) at 55 ° C, followed by washing with 2X SSPE and 0.1% SDS at 55 ° C or room temperature.

[0110] En otro aspecto, se proporciona un agente de unión que se une preferiblemente a un PRO que comprende una variación de aminoácido en relación con un PRO de tipo salvaje. En una realización, la variación de aminoácido es en una posición de aminoácido seleccionada de la figura 1 ó 3. En una de dichas realizaciones, la variación de aminoácido es un cambio de aminoácido seleccionado de la Figura 1 ó 3. En otra realización, el agente de unión es un anticuerpo. [0110] In another aspect, a binding agent is provided that preferably binds to a PRO comprising an amino acid variation in relation to a wild-type PRO. In one embodiment, the amino acid variation is at a selected amino acid position of Figure 1 or 3. In one such embodiment, the amino acid variation is a change of amino acid selected from Figure 1 or 3. In another embodiment, the binding agent is an antibody.

[0111] En otro aspecto, se proporcionan kits de diagnóstico. En una realización, un kit comprende cualquiera de los polinucleótidos anteriores y una enzima. En una realización, la enzima es por lo menos una enzima seleccionada entre una nucleasa, una ligasa y una polimerasa. [0111] In another aspect, diagnostic kits are provided. In one embodiment, a kit comprises any of the above polynucleotides and an enzyme. In one embodiment, the enzyme is at least one enzyme selected from a nuclease, a ligase and a polymerase.

C. Métodos C. Methods

[0112] En un aspecto, se proporciona un método de detección de la presencia de un tumor, comprendiendo el método detectar una variación en un PRO o polinucleótido PRO derivado de una muestra biológica. En una realización, la muestra biológica se obtiene de un mamífero sospechoso de tener un tumor. [0112] In one aspect, a method of detecting the presence of a tumor is provided, the method comprising detecting a variation in a PRO or PRO polynucleotide derived from a biological sample. In one embodiment, the biological sample is obtained from a mammal suspected of having a tumor.

[0113] En otro aspecto, se proporciona un método de determinación del genotipo de una muestra biológica, comprendiendo el método detectar si una variación de nucleótido está presente en un polinucleótido de PRO derivado de la muestra biológica. En una realización, la variación de nucleótido es en una posición de nucleótido seleccionada de las figuras 1-3. En una de dichas realizaciones, la variación de nucleótido es un cambio de nucleótido seleccionado de las figuras 1-3. En otra realización, la muestra biológica es sospechosa de comprender células tumorales. En otra realización, la muestra biológica es una línea celular, por ejemplo, una línea celular inmortalizada. En otra realización, la muestra biológica es un tumor. En una de dichas realizaciones, la búsqueda de genotipo del tumor proporciona una base para la clasificación del tumor. [0113] In another aspect, a method of determining the genotype of a biological sample is provided, the method comprising detecting if a nucleotide variation is present in a PRO polynucleotide derived from the biological sample. In one embodiment, the nucleotide variation is in a nucleotide position selected from Figures 1-3. In one such embodiment, the nucleotide variation is a nucleotide change selected from Figures 1-3. In another embodiment, the biological sample is suspected of comprising tumor cells. In another embodiment, the biological sample is a cell line, for example, an immortalized cell line. In another embodiment, the biological sample is a tumor. In one such embodiment, the tumor genotype search provides a basis for tumor classification.

[0114] En otro aspecto, se proporciona un método de identificación de células tumorales en una muestra biológica de un mamífero, comprendiendo el método detectar una variación en un PRO o polinucleótido PRO derivado de la muestra biológica. En una realización, la variación es una variación de nucleótido. En una de dichas realizaciones, la variación de nucleótido es en una posición de nucleótido seleccionada de las figuras 1-3. En una de dichas realizaciones, la variación de nucleótido es un cambio de nucleótido seleccionado de las figuras 1-3. En otra realización, la variación es una variación de aminoácido. En una de dichas realizaciones, la variación de aminoácido está en un dominio funcional de PRO seleccionado de la figura 1 ó 3. En otra de dichas realizaciones, la variación de aminoácido es en una posición de aminoácido seleccionada de la figura 1 ó 3. En otra de dichas realizaciones, la variación de aminoácido es un cambio de aminoácido seleccionado de la figura 1 ó 3. En otra realización, la muestra biológica es una biopsia (por ejemplo, una muestra de tejido que contiene células sospechosas de ser cancerosas). [0114] In another aspect, a method of identifying tumor cells in a biological sample of a mammal is provided, the method comprising detecting a variation in a PRO or PRO polynucleotide derived from the biological sample. In one embodiment, the variation is a nucleotide variation. In one of said embodiments, the nucleotide variation is in a nucleotide position selected from Figures 1-3. In one such embodiment, the nucleotide variation is a nucleotide change selected from Figures 1-3. In another embodiment, the variation is an amino acid variation. In one of said embodiments, the amino acid variation is in a functional domain of PRO selected from Figure 1 or 3. In another of said embodiments, the amino acid variation is in a selected amino acid position of Figure 1 or 3. In Another such embodiment, the amino acid variation is an amino acid change selected from Figure 1 or 3. In another embodiment, the biological sample is a biopsy (for example, a tissue sample containing cells suspected of being cancerous).

[0115] En otro aspecto, se proporciona un método de diagnóstico de un tumor en un mamífero, comprendiendo el método detectar la presencia de una variación en un PRO o polinucleótido PRO derivado de una muestra biológica obtenida del mamífero, en el que la muestra biológica es conocida o sospechosa de comprender células tumorales. En una realización, la variación es una variación de nucleótido. En una de dichas realizaciones, la variación de nucleótido es en una posición de nucleótido seleccionada de las figuras 1-3. En una de dichas realizaciones, la variación de nucleótido es un cambio de nucleótido seleccionado de las figuras 1-3. En otra realización, la variación es una variación de aminoácidos. En una de dichas realizaciones, la variación de aminoácido está en un dominio funcional de PRO seleccionado de la figura 1 ó 3. En otra de dichas realizaciones, la variación de aminoácido es en una posición de aminoácido seleccionada de la figura 1 ó 3. En otra de dichas realizaciones, la variación de aminoácido es un cambio de aminoácido seleccionado de la figura 1 ó 3. En otra realización, el método es un método de clasificación de un tumor, por ejemplo, como un tumor caracterizado por una variación o variaciones de nucleótido o aminoácido en un polinucleótido de PRO o PRO particular. [0115] In another aspect, a method of diagnosing a tumor in a mammal is provided, the method comprising detecting the presence of a variation in a PRO or PRO polynucleotide derived from a biological sample obtained from the mammal, in which the biological sample It is known or suspected of understanding tumor cells. In one embodiment, the variation is a nucleotide variation. In one of said embodiments, the nucleotide variation is in a nucleotide position selected from Figures 1-3. In one such embodiment, the nucleotide variation is a nucleotide change selected from Figures 1-3. In another embodiment, the variation is a variation of amino acids. In one of said embodiments, the amino acid variation is in a functional domain of PRO selected from Figure 1 or 3. In another of said embodiments, the amino acid variation is in a selected amino acid position of Figure 1 or 3. In Another such embodiment, the amino acid variation is an amino acid change selected from Figure 1 or 3. In another embodiment, the method is a method of classifying a tumor, for example, as a tumor characterized by a variation or variations of nucleotide or amino acid in a particular PRO or PRO polynucleotide.

[0116] En otro aspecto, se proporciona un método para predecir si un tumor de un mamífero responderá a un agente terapéutico que reconoce un PRO o polinucleótido de PRO, comprendiendo el método determinar si el tumor comprende una variación en un PRO o polinucleótido PRO, en el que la presencia de una variación en un PRO o polinucleótido PRO indica que el tumor responderá al agente terapéutico. En una realización, la variación es una variación de nucleótido. En una de dichas realizaciones, la variación de nucleótido es en una posición de nucleótido seleccionada de las figuras 1-3. En una de dichas realizaciones, la variación de nucleótido es un cambio de nucleótido seleccionado de las figuras 1-3. En otra realización, la variación es una variación de aminoácido. En una de dichas realizaciones, la variación de aminoácido está en un dominio funcional de PRO seleccionado de la figura 1 ó 3. En otra de dichas realizaciones, la variación de aminoácido es en una posición de aminoácido seleccionada de la figura 1 ó 3. En otra de dichas realizaciones, la variación de aminoácido es un cambio de aminoácido seleccionado de la figura 1 ó 3. En otra realización, la PRO es una quinasa (tal como una tirosina quinasa, por ejemplo, una RTK). En otra realización, la PRO es un supresor de tumor. [0116] In another aspect, a method is provided to predict whether a mammalian tumor will respond to a therapeutic agent that recognizes a PRO or PRO polynucleotide, the method comprising determining whether the tumor comprises a variation in a PRO or PRO polynucleotide, wherein the presence of a variation in a PRO or PRO polynucleotide indicates that the tumor will respond to the therapeutic agent. In one embodiment, the variation is a nucleotide variation. In one of said embodiments, the nucleotide variation is in a nucleotide position selected from Figures 1-3. In one such embodiment, the nucleotide variation is a nucleotide change selected from Figures 1-3. In another embodiment, the variation is an amino acid variation. In one of said embodiments, the amino acid variation is in a functional domain of PRO selected from Figure 1 or 3. In another of said embodiments, the amino acid variation is in a selected amino acid position of Figure 1 or 3. In Another such embodiment, the amino acid variation is an amino acid change selected from Figure 1 or 3. In another embodiment, the PRO is a kinase (such as a tyrosine kinase, for example, an RTK). In another embodiment, the PRO is a tumor suppressor.

[0117] En otro aspecto, se proporciona un método de detección de la ausencia o presencia de una variación de nucleótido en una posición de nucleótido en un ácido nucleico que codifica un PRO, comprendiendo el método (a) poner en contacto el ácido nucleico con cualquiera de los polinucleótidos descritos anteriormente (sección II.B.) bajo condiciones adecuadas para la formación de un complejo de hibridación entre el ácido nucleico y el polinucleótido; y [0117] In another aspect, there is provided a method of detecting the absence or presence of a nucleotide variation at a nucleotide position in a nucleic acid encoding a PRO, the method comprising (a) contacting the nucleic acid with any of the polynucleotides described above (section II.B.) under conditions suitable for the formation of a hybridization complex between the nucleic acid and the polynucleotide; Y

(b) detectar si el polinucleótidos se empareja específicamente en las bases con el ácido nucleico en la posición de nucleótido. En una realización, la variación de nucleótido es en una posición de nucleótido seleccionada de las figuras 1-3. En una de dichas realizaciones, la variación de nucleótido es un cambio de nucleótido seleccionado de las figuras 1-3. (b) detect if the polynucleotides are specifically matched in the bases with the nucleic acid in the nucleotide position. In one embodiment, the nucleotide variation is in a nucleotide position selected from Figures 1-3. In one such embodiment, the nucleotide variation is a nucleotide change selected from Figures 1-3.

[0118] En otro aspecto, se proporciona un método de detección de la ausencia o presencia de una variación de nucleótido en un ácido nucleico que codifica un PRO, comprendiendo el método (a) poner en contacto el ácido nucleico con un oligonucleótido específico de alelo que es específico para la variación de nucleótido bajo condiciones adecuadas para la hibridación del oligonucleótido específico de alelo al ácido nucleico; y (b) detectar la ausencia o presencia de la hibridación específica de alelo. En una realización, la variación de nucleótido es en una posición de nucleótido seleccionada de las figuras 1-3. En una de dichas realizaciones, la variación de nucleótido es un cambio de nucleótido seleccionado de las figuras 1-3. En otra realización, un oligonucleótido específico de alelo es un cebador específico de alelo. [0118] In another aspect, a method of detecting the absence or presence of a nucleotide variation in a nucleic acid encoding a PRO is provided, the method comprising (a) contacting the nucleic acid with an allele-specific oligonucleotide. which is specific for nucleotide variation under conditions suitable for hybridization of the allele-specific oligonucleotide to the nucleic acid; and (b) detect the absence or presence of allele specific hybridization. In one embodiment, the nucleotide variation is in a nucleotide position selected from Figures 1-3. In one such embodiment, the nucleotide variation is a nucleotide change selected from Figures 1-3. In another embodiment, an allele specific oligonucleotide is an allele specific primer.

[0119] En otro aspecto, se proporciona un método de amplificación de ácido nucleico que comprende un polinucleótido de PRO o un fragmento del mismo, en el que el polinucleótido de PRO o fragmento del mismo comprende una variación de nucleótido, comprendiendo el método (a) poner en contacto el ácido nucleico con un cebador que se hibrida a una secuencia 3’ de la variación de nucleótido, y (b) extender el cebador para generar un producto de amplificación que comprende la variación de nucleótido. En una realización, el método comprende además poner en contacto el producto de amplificación con un segundo cebador que se hibrida a una secuencia 3’ de la variación de nucleótido, y extender el segundo cebador para generar un segundo producto de amplificación. En una de dichas realizaciones, el método comprende además amplificar el producto de amplificación y el segundo producto de amplificación, por ejemplo, mediante PCR. En cualquiera de las realizaciones anteriores, la variación de nucleótido es en una posición de nucleótido seleccionada de las figuras 1-3. En cualquiera de las realizaciones anteriores, la variación de nucleótido es un cambio de nucleótido seleccionado de las figuras 1-3. [0119] In another aspect, a nucleic acid amplification method is provided comprising a PRO polynucleotide or a fragment thereof, wherein the PRO polynucleotide or fragment thereof comprises a nucleotide variation, the method comprising (a ) contacting the nucleic acid with a primer that hybridizes to a 3 'sequence of the nucleotide variation, and (b) extending the primer to generate an amplification product comprising the nucleotide variation. In one embodiment, the method further comprises contacting the amplification product with a second primer that hybridizes to a 3 'sequence of the nucleotide variation, and extending the second primer to generate a second amplification product. In one of said embodiments, the method further comprises amplifying the amplification product and the second amplification product, for example, by PCR. In any of the above embodiments, the nucleotide variation is in a nucleotide position selected from Figures 1-3. In any of the above embodiments, the nucleotide variation is a nucleotide change selected from Figures 1-3.

[0120] En otro aspecto, se proporciona un método de valoración de la actividad de un PRO que comprende una variación de aminoácido, comprendiendo el método (a) determinar la actividad del PRO; y (b) comparar la actividad del PRO con la actividad de un PRO de tipo salvaje. En una realización, la actividad es actividad de quinasa. En otra realización, la actividad es actividad supresora de tumor. En otra realización, la variación de aminoácido está en un dominio funcional de PRO seleccionado de la figura 1 ó 3. En otra realización, la variación de aminoácido es en una posición de aminoácido seleccionada de la figura 1 ó 3. En otra realización, la variación de aminoácido es un cambio de aminoácido seleccionado de la figura 1 ó 3. [0120] In another aspect, a method of assessing the activity of a PRO comprising an amino acid variation is provided, the method comprising (a) determining the activity of the PRO; and (b) compare the activity of the PRO with the activity of a wild-type PRO. In one embodiment, the activity is kinase activity. In another embodiment, the activity is tumor suppressor activity. In another embodiment, the amino acid variation is in a functional PRO domain selected from Figure 1 or 3. In another embodiment, the amino acid variation is at a selected amino acid position of Figure 1 or 3. In another embodiment, the Amino acid variation is a change of amino acid selected from Figure 1 or 3.

[0121] En otro aspecto, se proporciona un método de identificación de un agente para el tratamiento de un tumor, comprendiendo el método (a) poner en contacto un PRO con un agente de prueba, en el que el PRO comprende una variación de aminoácido, (b) valorar la actividad del PRO en presencia del agente de prueba con la actividad del PRO en ausencia del agente de prueba, en el que un incremento o descenso en la actividad del PRO en presencia del agente de prueba indica que el agente de prueba es un agente para el tratamiento de un tumor. En una realización, la variación de aminoácido está en un dominio funcional de PRO seleccionado de la figura 1 ó 3. En otra realización, la variación de aminoácido es en una posición de aminoácido seleccionada entre la figura 1 ó 3. En otra realización, la variación de aminoácido es un cambio de aminoácido seleccionado de la figura 1 ó 3. En otra realización, el PRO es una quinasa (tal como una tirosina quinasa, por ejemplo, una RTK), y un descenso en la actividad de la quinasa en presencia del agente de prueba indica que el agente de prueba es un agente para el tratamiento de un tumor. En otra realización, el PRO es un supresor de tumores, y un incremento en la actividad del supresor de tumores en presencia del agente de prueba indica que el agente de prueba es un agente para el tratamiento de un tumor. [0121] In another aspect, there is provided a method of identifying an agent for the treatment of a tumor, the method comprising (a) contacting a PRO with a test agent, wherein the PRO comprises an amino acid variation , (b) assess the activity of the PRO in the presence of the test agent with the activity of the PRO in the absence of the test agent, in which an increase or decrease in the activity of the PRO in the presence of the test agent indicates that the Test is an agent for the treatment of a tumor. In one embodiment, the amino acid variation is in a functional domain of PRO selected from Figure 1 or 3. In another embodiment, the amino acid variation is in an amino acid position selected from Figure 1 or 3. In another embodiment, the Amino acid variation is a change of amino acid selected from Figure 1 or 3. In another embodiment, the PRO is a kinase (such as a tyrosine kinase, for example, an RTK), and a decrease in kinase activity in the presence The test agent indicates that the test agent is an agent for the treatment of a tumor. In another embodiment, the PRO is a tumor suppressor, and an increase in tumor suppressor activity in the presence of the test agent indicates that the test agent is an agent for the treatment of a tumor.

[0122] En otro aspecto, se proporciona un método de inhibición de la proliferación de una célula tumoral, en el que la célula tumoral comprende un PRO que tiene una variación activante, comprendiendo el método exponer la célula tumoral a un antagonista de PRO. En una realización, el PRO es una quinasa, por ejemplo, un receptor tirosina quinasa. [0122] In another aspect, a method of inhibiting the proliferation of a tumor cell is provided, in which the tumor cell comprises a PRO having an activating variation, the method comprising exposing the tumor cell to a PRO antagonist. In one embodiment, the PRO is a kinase, for example, a tyrosine kinase receptor.

[0123] En otro aspecto, se proporciona un método de inhibición de la proliferación de una célula tumoral, en el que la célula tumoral comprende una variación en un PRO que disminuye la actividad de PRO, comprendiendo el método exponer la célula tumoral a un agonista de PRO. En una realización, un agonista comprende un polinucleótido de PRO o el propio PRO. En otras realizaciones, el PRO es un supresor de tumores. [0123] In another aspect, a method of inhibiting the proliferation of a tumor cell is provided, in which the tumor cell comprises a variation in a PRO that decreases the activity of PRO, the method comprising exposing the tumor cell to an agonist. of PRO. In one embodiment, an agonist comprises a PRO polynucleotide or the PRO itself. In other embodiments, the PRO is a tumor suppressor.

[0124] En otro aspecto, se proporciona un método de tratamiento comprende una variación en un PRO, comprendiendo el método administrar a un mamífero que tiene el tumor una cantidad efectiva de una formulación farmacéutica que comprende un antagonista o agonista de PRO. En una realización, la variación es una variación de nucleótido. En una de dichas realizaciones, la variación de nucleótido es en una posición de nucleótido seleccionada de las figuras 1-3. En una de dichas realizaciones, la variación de nucleótido es un cambio de nucleótido seleccionado de las figuras 1-3. En otra realización, la variación es una variación de aminoácido. En una de dichas realizaciones, la variación de aminoácido está en un dominio funcional de PRO seleccionado de la figura 1 ó 3. En otra de dichas realizaciones, la variación de aminoácido es en una posición de aminoácido seleccionada de la figura 1 ó 3. En otra de dichas realizaciones, la variación de aminoácido es un cambio de aminoácido seleccionado de la figura 1 ó 3. En otra realización, el PRO es una quinasa (tal como una tirosina quinasa, por ejemplo, un RTK). En otra realización, el PRO es un supresor de tumores. [0124] In another aspect, a method of treatment is provided comprising a variation in a PRO, the method comprising administering to a mammal having the tumor an effective amount of a pharmaceutical formulation comprising a PRO antagonist or agonist. In one embodiment, the variation is a nucleotide variation. In one of said embodiments, the nucleotide variation is in a nucleotide position selected from Figures 1-3. In one such embodiment, the nucleotide variation is a nucleotide change selected from Figures 1-3. In another embodiment, the variation is an amino acid variation. In one of said embodiments, the amino acid variation is in a functional domain of PRO selected from Figure 1 or 3. In another of said embodiments, the amino acid variation is in a selected amino acid position of Figure 1 or 3. In Another such embodiment, the amino acid variation is an amino acid change selected from Figure 1 or 3. In another embodiment, the PRO is a kinase (such as a tyrosine kinase, for example, an RTK). In another embodiment, the PRO is a tumor suppressor.

[0125] Un tumor, según cualquiera de los métodos anteriores, puede ser un tumor seleccionado entre un tumor de pulmón (particularmente carcinomas de pulmón de célula no pequeña), tumor de mama, tumor de colon, tumor de riñón, tumor de hígado, tumor de vejiga, tumor de ovario, tumor de estómago, tumor de piel (incluyendo cánceres de piel con melanoma y sin melanoma), y linfoma. En una realización, un tumor es un tumor de pulmón, un carcinoma de pulmón de célula no pequeña [0125] A tumor, according to any of the above methods, may be a tumor selected from a lung tumor (particularly non-small cell lung carcinomas), breast tumor, colon tumor, kidney tumor, liver tumor, Bladder tumor, ovarian tumor, stomach tumor, skin tumor (including skin cancers with melanoma and without melanoma), and lymphoma. In one embodiment, a tumor is a lung tumor, a non-small cell lung carcinoma.

[0126] Una variación de nucleótido, según cualquiera de los métodos anteriores, puede ser una mutación somática o un polimorfismo en la línea germinal. [0126] A nucleotide variation, according to any of the above methods, may be a somatic mutation or a germline polymorphism.

D. Técnicas generales D. General techniques

[0127] El ácido nucleico, según cualquiera de los métodos anteriores, puede ser ADN genómico; ARN transcrito a partir de ADN genómico; o ADNc generado a partir de ARN. El ácido nucleico puede derivarse de un vertebrado, por ejemplo, un mamífero. Se dice que un ácido nucleico "deriva de" un origen concreto si se obtiene directamente de ese origen o si es una copia de un ácido nucleico hallado en ese origen. [0127] The nucleic acid, according to any of the above methods, may be genomic DNA; RNA transcribed from genomic DNA; or cDNA generated from RNA. The nucleic acid can be derived from a vertebrate, for example, a mammal. It is said that a nucleic acid " derives from " a specific origin if obtained directly from that origin or if it is a copy of a nucleic acid found in that origin.

[0128] El ácido nucleico incluye copias del ácido nucleico, por ejemplo, copias que resultan de la amplificación. La amplificación puede ser deseable en ciertos casos, por ejemplo, con el objetivo de obtener una cantidad deseada de material para la detección de variaciones. Por ejemplo, puede amplificarse un polinucleótido de PRO o una parte del mismo a partir del material de ácido nucleico. A continuación, los amplicones pueden someterse a un método de detección de variación, tales como los descritos más adelante, para determinar si una variación está presente en el amplicón. [0128] The nucleic acid includes copies of the nucleic acid, for example, copies resulting from amplification. Amplification may be desirable in certain cases, for example, in order to obtain a desired amount of material for the detection of variations. For example, a PRO polynucleotide or a part thereof can be amplified from the nucleic acid material. The amplicons can then be subjected to a variation detection method, such as those described below, to determine if a variation is present in the amplicon.

[0129] Las variaciones pueden detectarse mediante ciertos métodos conocidos por los expertos en la materia. Dichos métodos incluyen, pero sin limitación, secuenciación de ADN; ensayos de extensión con cebador, que incluyen ensayos de incorporación de nucleótidos específicos de alelo y ensayos de extensión con cebador específicos de alelo (por ejemplo, PCR específico de alelo, reacción en cadena de unión específica de alelo (LCR), y gap-LCR); ensayos de hibridación de oligonucleótido específico de alelo (por ejemplo, ensayos de unión de oligonucleótidos); ensayos de protección de la división en los que se utiliza la protección de los agentes de la división para detectar bases mal emparejadas en las cadenas dobles de ácido nucleico; análisis de unión de proteínas MutS; análisis electroforético que compara la movilidad de moléculas de ácido nucleico de tipo salvaje y variantes; electroforesis en gel con gradiente de desnaturalización (DGGE, como en, por ejemplo, Myers et al. (1985) Nature 313:495); análisis de la división de ARNasa en pares de bases mal emparejadas; análisis de la división química o enzimática de ADN en heterocadenas dobles; espectrometría de masas (por ejemplo, MALDI-TOF); análisis de bit genético (GBA); ensayos de 5’ nucleasa (por ejemplo, TaqMan®); y ensayos que emplean sondas fluorescentes. A continuación, se discuten en mayor detalle algunos de estos métodos. [0129] Variations can be detected by certain methods known to those skilled in the art. Such methods include, but are not limited to DNA sequencing; primer extension assays, including allele specific nucleotide incorporation assays and allele specific primer extension assays (eg, allele specific PCR, allele specific binding chain reaction (CSF), and gap-CSF ); allele specific oligonucleotide hybridization assays (eg, oligonucleotide binding assays); division protection assays in which the protection of division agents is used to detect mismatched bases in double nucleic acid chains; MutS protein binding analysis; electrophoretic analysis comparing the mobility of wild-type nucleic acid molecules and variants; gel electrophoresis with gradient denaturation (DGGE, as in, for example, Myers et al. (1985) Nature 313: 495); RNAse division analysis in mismatched base pairs; analysis of the chemical or enzymatic division of DNA into double hetero chains; mass spectrometry (for example, MALDI-TOF); genetic bit analysis (GBA); 5 ’nuclease assays (eg, TaqMan®); and assays using fluorescent probes. Next, some of these methods are discussed in greater detail.

[0130] La detección de variaciones en ácidos nucleicos diana puede realizarse mediante clonación molecular y secuenciación de los ácidos nucleicos diana utilizando técnicas bien conocidas en el sector. De modo alternativo, pueden utilizarse técnicas de amplificación, tales como la reacción en cadena de la polimerasa (PCR) para amplificar las secuencias de ácido nucleico diana directamente a partir de una preparación de ADN genómico de un tejido tumoral. A continuación, puede determinarse la secuencia de ácido nucleico de las secuencias amplificadas y las variaciones identificadas de la misma. Las técnicas de amplificación son bien conocidas en el sector, por ejemplo, se describe la reacción en cadena de la polimerasa en Saiki et al., Science 239:487, 1988; Patentes de Estados Unidos Nº 4.683.203 y 4.683.195. [0130] The detection of variations in target nucleic acids can be performed by molecular cloning and sequencing of the target nucleic acids using techniques well known in the art. Alternatively, amplification techniques, such as polymerase chain reaction (PCR) can be used to amplify the target nucleic acid sequences directly from a genomic DNA preparation of a tumor tissue. Next, the nucleic acid sequence of the amplified sequences and the identified variations thereof can be determined. Amplification techniques are well known in the sector, for example, the polymerase chain reaction is described in Saiki et al., Science 239: 487, 1988; U.S. Patents No. 4,683,203 and 4,683,195.

[0131] La reacción en cadena de ligasa, que es conocida en la técnica, también puede utilizarse para amplificar secuencias de ácido nucleico diana. Ver, por ejemplo, Wu et al., Genomics 4:560-569 (1989). Además, también puede utilizarse una técnica conocida como PCR específica de alelo para detectar variaciones (por ejemplo, substituciones). Ver, por ejemplo, Ruano y Kidd (1989) Nucleic Acids Research 17:8392; McClay et al. (2002) Analytical Biochem. 301:200-206. En algunas realizaciones de esta técnica, se utiliza un cebador específico de alelo en el que el nucleótido 3’ terminal del cebador es complementario a (es decir, capaz de emparejar bases específicamente con) una variación concreta en el ácido nucleico diana. Si la variación concreta no está presente, no se observa producto de amplificación. También puede utilizarse el Sistema de Amplificación Refractoria de Mutaciones (ARMS) para detectar variaciones (por ejemplo, substituciones). El ARMS se describe, por ejemplo, en la Publicación de Solicitud de Patente Europea nº 0332435, y en Newton et al., Nucleic Acids Research, 17:7, 1989. [0131] The ligase chain reaction, which is known in the art, can also be used to amplify target nucleic acid sequences. See, for example, Wu et al., Genomics 4: 560-569 (1989). In addition, a technique known as allele-specific PCR can also be used to detect variations (eg substitutions). See, for example, Ruano and Kidd (1989) Nucleic Acids Research 17: 8392; McClay et al. (2002) Analytical Biochem. 301: 200-206. In some embodiments of this technique, an allele-specific primer is used in which the 3 'terminal nucleotide of the primer is complementary to (i.e., capable of pairing bases specifically with) a specific variation in the target nucleic acid. If the concrete variation is not present, no amplification product is observed. The Refractory Mutation Amplification System (ARMS) can also be used to detect variations (eg substitutions). ARMS is described, for example, in European Patent Application Publication No. 0332435, and in Newton et al., Nucleic Acids Research, 17: 7, 1989.

[0132] Otros métodos útiles para detectar variaciones (por ejemplo, substituciones) incluyen, pero sin limitación, (1) ensayos de incorporación de nucleótido específico de alelo, como los ensayos de extensión con una sola base (ver, por ejemplo, Chen et al. (2000) Genome Res. 10:549-557; Fan et al. (2000) Genome Res. 10:853-860; Pastinen et al. (1997) Genome Res. 7:606-614; y Ye et al. (2001) Hum. Mut. 17:305-316); (2) ensayos de extensión con cebador específico de alelo (ver, por ejemplo, Ye et al. (2001) Hum. Mut. 17:305-316; y Shen et al. Genetic Engineering News, vol. 23, Mar. 15, 2003), incluyendo PCR específico de alelo; (3) ensayos de 5’ nucleasa (ver, por ejemplo, De La Vega et al. (2002) BioTechniques 32:S48-S54 (que describe el ensayo TaqMan®); Ranade et al. (2001) Genome Res. 11:1262-1268; y Shi (2001) Clin. Chem. 47:164-172); (4) ensayos que emplean sondas fluorescentes (ver, por ejemplo, Tyagi et al. (1998) Nature Biotech. 16:49-53; y Mhlanga et al. (2001) Methods 25: 463-71); y (5) ensayos de unión de oligonucleótido (ver, por ejemplo, Grossman et al. (1994) Nuc. Acids Res. 22:4527-4534; publicación de solicitud de patente nº US 2003/0119004 Al; publicación internacional PCT nº WO 01/92579 A2; y patente de Estados Unidos nº 6.027.889). [0132] Other methods useful for detecting variations (eg substitutions) include, but are not limited to (1) allele-specific nucleotide incorporation assays, such as single-base extension assays (see, for example, Chen et al. (2000) Genome Res. 10: 549-557; Fan et al. (2000) Genome Res. 10: 853-860; Pastinen et al. (1997) Genome Res. 7: 606-614; and Ye et al . (2001) Hum. Mut. 17: 305-316); (2) allele-specific extension assays (see, for example, Ye et al. (2001) Hum. Mut. 17: 305-316; and Shen et al. Genetic Engineering News, vol. 23, Mar. 15 , 2003), including allele-specific PCR; (3) 5 'nuclease assays (see, for example, De La Vega et al. (2002) BioTechniques 32: S48-S54 (which describes the TaqMan® assay); Ranade et al. (2001) Genome Res. 11: 1262-1268; and Shi (2001) Clin. Chem. 47: 164-172); (4) assays using fluorescent probes (see, for example, Tyagi et al. (1998) Nature Biotech. 16: 49-53; and Mhlanga et al. (2001) Methods 25: 463-71); and (5) oligonucleotide binding assays (see, for example, Grossman et al. (1994) Nuc. Acids Res. 22: 4527-4534; Patent Application Publication No. US 2003/0119004 Al; PCT International Publication No. WO 01/92579 A2; and U.S. Patent No. 6,027,889).

[0133] También pueden detectarse variaciones mediante métodos de detección de apareamientos erróneos. Los apareamientos erróneos son cadenas dobles de ácido nucleico hibridadas que no son complementarias al 100%. La falta de complementariedad total puede deberse a deleciones, inserciones, inversiones, o substituciones. Un ejemplo de un método de detección de apareamiento erróneo es el ensayo de Detección de Reparación de Apareamiento Erróneo (MRD) descrito, por ejemplo, en Faham et al., Proc. Natl Acad. Sci. USA 102:14717-14722 (2005) y Faham et al., Hum. Mol. Genet. 10:1657-1664 (2001). Otro ejemplo de una técnica de división de apareamiento erróneo es el método de protección de ARNasa, que se describe en detalle en Winter et al., Proc. Natl. Acad. Sci. USA, 82:7575, 1985, y Myers et al., Science 230: 1242, 1985. Por ejemplo, un método de la invención puede implicar el uso de una ribosonda marcada que es complementaria al ácido nucleico diana de tipo salvaje humano. La ribosonda y el ácido nucleico diana derivado de la muestra de tejido se hibridan juntos y posteriormente se digieren con la enzima ARNasa A que es capaz de detectar algunos apareamientos erróneos en una estructura de ARN de cadena doble. Si se detecta un apareamiento erróneo mediante ARNasa A, se divide en el sitio del apareamiento erróneo. De este modo, cuando se separa la preparación de ARN hibridada en una matriz de gel electroforético, si se ha detectado un apareamiento erróneo y se ha dividido mediante ARNasa A, se observará un producto de ARN que es más pequeño que el ARN de cadena doble de longitud completa para la ribosonda y el ARNm o el ADN. La ribosonda no necesita ser la longitud completa del ácido nucleico diana, pero puede ser una parte del ácido nucleico diana, siempre que comprenda la posición sospechosa de tener una variación. [0133] Variations can also be detected by methods of detecting mismatches. Mismatches are double hybridized nucleic acid chains that are not 100% complementary. The lack of total complementarity may be due to deletions, insertions, investments, or substitutions. An example of a mismatch detection method is the Erroneous Mating Repair Detection (MRD) test described, for example, in Faham et al., Proc. Natl Acad. Sci. USA 102: 14717-14722 (2005) and Faham et al., Hum. Mol. Genet 10: 1657-1664 (2001). Another example of a mating division technique is the RNAse protection method, which is described in detail in Winter et al., Proc. Natl Acad. Sci. USA, 82: 7575, 1985, and Myers et al., Science 230: 1242, 1985. For example, a method of the invention may involve the use of a labeled ribosonde that is complementary to the human wild type target nucleic acid. . The ribosonde and the target nucleic acid derived from the tissue sample are hybridized together and subsequently digested with the enzyme RNase A which is able to detect some mismatches in a double stranded RNA structure. If a mismatch is detected by RNase A, it is divided at the site of the wrong match. Thus, when the hybridized RNA preparation is separated on an electrophoretic gel matrix, if an erroneous pairing has been detected and divided by RNase A, an RNA product that is smaller than the double stranded RNA will be observed. full length for ribosonde and mRNA or DNA. The ribosonde does not need to be the full length of the target nucleic acid, but it can be a part of the target nucleic acid, provided it understands the position suspected of having a variation.

[0134] De una manera similar, pueden utilizarse sondas de ADN para detectar apareamientos erróneos, por ejemplo a través de división enzimática o química. Ver, por ejemplo, Cotton et al., Proc. Natl. Acad. Sci. USA, 85:4397, 1988: y Shenk et al., Proc. Natl. Acad. Sci. USA, 72:989, 1975. De modo alternativo, pueden detectarse apareamientos erróneos mediante desplazamientos en la movilidad electroforética de cadenas dobles erróneamente apareadas en relación con cadenas dobles apareadas. Ver, por ejemplo, Cariello, Human Genetics, 42:726, 1988. Ya sea con ribosondas o sondas de ADN, el ácido nucleico diana sospechoso de comprender una variación puede amplificarse antes de la hibridación. También pueden detectarse cambios en el ácido nucleico diana utilizando hibridación Southern, especialmente si los cambios son reorganizaciones bruscas, tales como deleciones e inserciones. [0134] Similarly, DNA probes can be used to detect mismatches, for example through enzymatic or chemical division. See, for example, Cotton et al., Proc. Natl Acad. Sci. USA, 85: 4397, 1988: and Shenk et al., Proc. Natl Acad. Sci. USA, 72: 989, 1975. Alternatively, erroneous pairings can be detected by electrophoretic mobility shifts of double strands mistakenly paired in relation to paired double strands. See, for example, Cariello, Human Genetics, 42: 726, 1988. Whether with ribosonde or DNA probes, the target nucleic acid suspected of understanding a variation can be amplified before hybridization. Changes in the target nucleic acid can also be detected using Southern hybridization, especially if the changes are abrupt reorganizations, such as deletions and insertions.

[0135] Las sondas de polimorfismo de longitud de un fragmento de restricción (RFLP) para el ácido nucleico diana o los genes marcadores de alrededor pueden utilizarse para detectar variaciones, por ejemplo, inserciones o deleciones. También pueden detectarse inserciones y deleciones mediante clonación, secuenciación y amplificación de un ácido nucleico diana. También puede utilizarse un análisis de polimorfismo de conformación de una sola cadena (SSCP) para detectar variantes de cambios de bases de un alelo. Ver, por ejemplo Orita et al., Proc. Natl. Acad. Sci. USA 86:2766-2770, 1989, y Genomics, 5:874-879, 1989. [0135] Restriction fragment length polymorphism (RFLP) probes for the target nucleic acid or surrounding marker genes can be used to detect variations, for example, insertions or deletions. Insertions and deletions can also be detected by cloning, sequencing and amplification of a target nucleic acid. A single chain conformation polymorphism (SSCP) analysis can also be used to detect base change variants of an allele. See, for example Orita et al., Proc. Natl Acad. Sci. USA 86: 2766-2770, 1989, and Genomics, 5: 874-879, 1989.

[0136] La invención también proporciona una variedad de composiciones aptas para su uso en la realización de métodos de la invención. Por ejemplo, la invención proporciona arrays que pueden utilizarse en dichos métodos. En una realización, un array de la invención comprende colecciones de moléculas de ácido nucleico o de forma individual para detectar variaciones de la invención. Por ejemplo, un array de la invención puede comprender una serie de oligonucleótidos específicos de alelo individuales colocados discretamente o conjuntos de oligonucleótidos específicos de alelo. Se conocen bien diversas técnicas en el sector para unir ácidos nucleicos a un sustrato sólido, tal como un portaobjetos de vidrio. Un método es incorporar bases modificadas o análogos que contienen una parte reactiva que es capaz de unirse a un sustrato sólido, tal como un grupo amino, un derivado de un grupo amino, u otro grupo con una carga positiva, en las moléculas de ácido nucleico que se sintetizan. A continuación, se pone en contacto el producto sintetizado con un sustrato sólido, tal como un portaobjetos de vidrio cubierto con un aldehído u otro grupo reactivo. El aldehido o el otro grupo reactivo formará un enlace covalente con la parte reactiva en el producto amplificado, que acabará uniéndose covalentemente al portaobjetos de vidrio. Otros métodos son conocidos en la técnica, tales como los que utilizan química de superficie con amino propil sílica. [0136] The invention also provides a variety of compositions suitable for use in carrying out methods of the invention. For example, the invention provides arrays that can be used in such methods. In one embodiment, an array of the invention comprises collections of nucleic acid molecules or individually to detect variations of the invention. For example, an array of the invention may comprise a series of discretely placed individual allele oligonucleotides or sets of allele specific oligonucleotides. Various techniques are well known in the sector for attaching nucleic acids to a solid substrate, such as a glass slide. One method is to incorporate modified bases or analogs containing a reactive part that is capable of binding to a solid substrate, such as an amino group, a derivative of an amino group, or another group with a positive charge, in the nucleic acid molecules. They are synthesized. Next, the synthesized product is contacted with a solid substrate, such as a glass slide covered with an aldehyde or other reactive group. The aldehyde or the other reactive group will form a covalent bond with the reactive part in the amplified product, which will end up covalently binding to the glass slide. Other methods are known in the art, such as those using surface chemistry with amino propyl silica.

[0137] Según cualquiera de los métodos anteriores, puede obtenerse una muestra biológica utilizando ciertos métodos conocidos por los expertos en la materia. Las muestras biológicas pueden obtenerse de animales vertebrados, y en concreto, de mamíferos. Se utiliza frecuentemente la biopsia tisular para obtener un trozo representativo de tejido tumoral. De modo alternativo, pueden obtenerse células tumorales indirectamente en forma de tejidos o fluidos que son conocidos o se cree que contienen las células tumorales de interés. Por ejemplo, pueden obtenerse muestras de lesiones de cáncer de pulmón mediante resección, broncoscopia, aspiración, raspados bronquiales o esputos, fluido pleural o sangre. Las variaciones en ácidos nucleicos diana (o polipéptidos codificados) pueden detectarse a partir de una muestra de tumor o de otras muestras corporales, tales como la orina, el esputo o el suero. (Las células cancerosas se desprenden de los tumores y aparecen en dichas muestras corporales.) Cribando tales muestras corporales, puede lograrse un diagnóstico simple y precoz para enfermedades, tales como el cáncer. Además, puede monitorizarse más fácilmente el progreso de la terapia mediante el análisis de dichas muestras corporales para variaciones en ácidos nucleicos diana (o polipéptidos codificados). Adicionalmente, los métodos para enriquecer una preparación de tejido para células tumorales son conocidos en la técnica. Por ejemplo, puede aislarse el tejido a partir de secciones de parafina o criostato. También pueden separarse las células cancerosas de las células normales mediante citometría de flujo o microdisección de captura de láser. [0137] According to any of the above methods, a biological sample can be obtained using certain methods known to those skilled in the art. Biological samples can be obtained from vertebrate animals, and specifically from mammals. Tissue biopsy is frequently used to obtain a representative piece of tumor tissue. Alternatively, tumor cells may be obtained indirectly in the form of tissues or fluids that are known or believed to contain the tumor cells of interest. For example, samples of lung cancer lesions can be obtained by resection, bronchoscopy, aspiration, bronchial or sputum scrapes, pleural fluid or blood. Variations in target nucleic acids (or encoded polypeptides) can be detected from a tumor sample or other body samples, such as urine, sputum or serum. (Cancer cells break away from tumors and appear in such body samples.) By screening such body samples, a simple and early diagnosis can be achieved for diseases, such as cancer. In addition, the progress of therapy can be more easily monitored by analyzing said body samples for variations in target nucleic acids (or encoded polypeptides). Additionally, methods for enriching a tissue preparation for tumor cells are known in the art. For example, tissue can be isolated from paraffin or cryostat sections. Cancer cells can also be separated from normal cells by flow cytometry or laser capture microdissection.

111. EJEMPLOS 111. EXAMPLES

[0138] Se obtuvieron veinticinco muestras diferentes de carcinoma de pulmón de célula no pequeña humanas (NSCLC) de fuentes comerciales. Se sometieron las muestras a revisión patológica para asegurar el contenido tumoral suficiente (es decir, de promedio >75% de células tumorales). Se analizaron cien genes según sus variaciones utilizando la Detección de Reparación de Apareamiento erróneo (MRD), y se analizó un subconjunto de esos genes independientemente utilizando secuenciación Sanger, tal y como se describe más adelante. Algunos de los 100 genes seleccionados se sabía o se sospechaba que jugaban un papel en el cáncer, y algunos no habían sido implicados previamente en la tumorigénesis o la progresión tumoral. [0138] Twenty-five different samples of human non-small cell lung carcinoma (NSCLC) were obtained from commercial sources. Samples were subjected to pathological review to ensure sufficient tumor content (i.e., on average> 75% of tumor cells). One hundred genes were analyzed according to their variations using the Mismatch Repair Repair (MRD), and a subset of those genes was analyzed independently using Sanger sequencing, as described below. Some of the 100 selected genes were known or suspected to play a role in cancer, and some had not previously been implicated in tumorigenesis or tumor progression.

A. Identificación de variaciones mediante MRD A. Identification of variations by MRD

[0139] Se utilizó Detección de Reparación de Apareamiento erróneo (MRD) para identificar variaciones de nucleótido en los genes seleccionados. Los detalles del método de MRD se describen en Faham et al., Proc. Natl Acad. Sci. USA 102:14717-14722 (2005) y Faham et al., Hum. Mol. Genet. 10:1657-1664 (2001). En resumen, se diseñaron cebadores de PCR para cada exón de interés. En el extremo 5’ de cada cebador directo de PCR se añadió una secuencia de 25 nucleótidos. Veintiuno de los nucleótidos constituyen una secuencia etiqueta específica para cada amplicón, y los cuatro pares de bases restantes forman un sitio de digestión de enzima de restricción HaeIII, que se utilizó al final para separar la etiqueta de la secuencia genómica antes de la etapa de detección de array. [0139] Wrong Pairing Repair Detection (MRD) was used to identify nucleotide variations in the selected genes. Details of the MRD method are described in Faham et al., Proc. Natl Acad. Sci. USA 102: 14717-14722 (2005) and Faham et al., Hum. Mol. Genet 10: 1657-1664 (2001). In summary, PCR primers were designed for each exon of interest. A 25 nucleotide sequence was added at the 5 ’end of each direct PCR primer. Twenty-one of the nucleotides constitute a specific tag sequence for each amplicon, and the remaining four base pairs form a HaeIII restriction enzyme digestion site, which was used at the end to separate the tag from the genomic sequence before the detection stage of array.

[0140] Se llevó a cabo la amplificación de PCR con cada par de cebadores utilizando el genoma de referencia homozigótico (mola hidatiforme) como plantilla. A continuación, se agruparon todos los amplicones y se clonaron en un plásmido para producir secuencias de referencia. Para las secuencias que llevaban un SNP común, se hizo un intento por crear dos patrones (con dos secuencias etiqueta distintas) correspondientes a cada uno de los dos alelos. Los mismos cebadores de PCR se utilizaron para PCR con multicadenas utilizando Pfu polimerasa (Stratagene, La Jolla, CA) de cada uno de los pares de ADN tumoral y ADN normal apareado. Se hibridaron los productos de PCR de muestras tumorales y muestras normales apareadas al conjunto de secuencias de referencia (además de un vector de control que carecía de secuencia genómica), dando lugar de ese modo a la formación de moléculas de ADN en heterocadenas con una cadena de la región genómica de interés del genoma de referencia y la otra de la muestra a analizar. [0140] PCR amplification was performed with each pair of primers using the homozygous reference genome (hydatidiform mole) as a template. Next, all amplicons were pooled and cloned into a plasmid to produce reference sequences. For sequences carrying a common SNP, an attempt was made to create two patterns (with two different tag sequences) corresponding to each of the two alleles. The same PCR primers were used for multi-chain PCR using Pfu polymerase (Stratagene, La Jolla, CA) of each of the pairs of tumor DNA and paired normal DNA. PCR products from tumor samples and normal samples paired to the set of reference sequences (in addition to a control vector lacking genomic sequence) were hybridized, thereby resulting in the formation of DNA molecules in hetero chains with a chain. of the genomic region of interest of the reference genome and the other of the sample to be analyzed.

[0141] A continuación se transformaron en masa las moléculas de heterocadenas en la cepa de E. coli de Mutation Sorter. La cepa de Mutation Sorter está manipulada de modo que las bacterias que reparan un apareamiento erróneo entre el ADN de referencia y el ADN que se analiza tienen un fenotipo de resistencia a antibiótico diferente de aquellos que no reparan. (Ver Faham et al., (2001) supra.) Después de la transformación, se desarrolló el cultivo bacteriano en dos medios diferentes para seleccionar los fragmentos variantes y no variantes. Se amplificó mediante PCR la minipreparación de ADN obtenida de los dos cultivos bacterianos seleccionados utilizando cebadores complementarios a la secuencia del vector. Los productos de la PCR se digirieron con HaeIII para separar la secuencia etiqueta del resto de la secuencia genómica y las etiquetas de los dos grupos se mezclaron y se hibridaron sobre un array en un ensayo de dos colores. Los fragmentos que eran idénticos a la muestra de referencia generaron señal fundamentalmente en el grupo no variante, mientras que aquellos que eran diferentes de la muestra de referencia tuvieron señal fundamentalmente en el grupo variante, y los fragmentos heterozigóticos generaron señal en ambos grupos. [0141] Subsequently, the hetero-chain molecules in the E. coli strain of Mutation Sorter were mass transformed. The strain of Mutation Sorter is manipulated so that the bacteria that repair a mismatch between the reference DNA and the DNA being analyzed have a different antibiotic resistance phenotype than those that do not repair. (See Faham et al., (2001) supra.) After transformation, the bacterial culture was developed in two different media to select the variant and non-variant fragments. The DNA mini-preparation obtained from the two bacterial cultures selected using primers complementary to the sequence of the vector was amplified by PCR. The PCR products were digested with HaeIII to separate the tag sequence from the rest of the genomic sequence and the tags of the two groups were mixed and hybridized on an array in a two-color assay. Fragments that were identical to the reference sample generated a signal primarily in the non-variant group, while those that were different from the reference sample had a signal primarily in the variant group, and heterozygous fragments generated signal in both groups.

[0142] Se determinó si las variaciones de nucleótidos identificadas mediante MRD eran mutaciones somáticas mediante la obtención del genotipo de muestras tumorales y normales apareadas utilizando una estrategia alternativa basada en espectrometría de masas, tal y como se describe en Nelson et al., Genome Res. 14:16641668. Se compararon las variaciones de nucleótido que se confirmaron que eran somáticas con mutaciones somáticas de la base de datos del Catálogo de Mutaciones Somáticas en el Cáncer (COSMIC) (ver Bamford et al. (2004) British Journal of Cancer 91:355-358). Se descubrieron doce variaciones de nucleótido somáticas en la base de datos COSMIC y no se describen en la presente invención. [0142] It was determined whether the nucleotide variations identified by MRD were somatic mutations by obtaining the genotype of paired tumor and normal samples using an alternative strategy based on mass spectrometry, as described in Nelson et al., Genome Res 14: 16641668. Nucleotide variations that were confirmed to be somatic were compared with somatic mutations from the Database of Somatic Mutations in Cancer (COSMIC) database (see Bamford et al. (2004) British Journal of Cancer 91: 355-358) . Twelve somatic nucleotide variations were discovered in the COSMIC database and are not described in the present invention.

[0143] En la Figura 1 se muestran las nuevas variaciones de nucleótido identificadas mediante MRD. La Figura 1 enumera las variaciones de nucleótido somáticas que son mutaciones no sinónimas o sin sentido. La Figura 2 enumera las variaciones de nucleótido somáticas que caen dentro de las regiones de sitio de empalme de consenso. Las Figuras 1 y 22 están descritas en mayor detalle anteriormente en la Descripción Detallada de las Realizaciones. [0143] Figure 1 shows the new nucleotide variations identified by MRD. Figure 1 lists the somatic nucleotide variations that are non-synonymous or nonsense mutations. Figure 2 lists the somatic nucleotide variations that fall within the consensus splice site regions. Figures 1 and 22 are described in greater detail above in the Detailed Description of the Embodiments.

[0144] Cabe destacar que la MRD identificó tres mutaciones somáticas en el dominio WD40 del gen FBXW7 (ver Variación ID Nº 10007, 10008, y 10009). Se sabe que FBXW7 es un supresor de tumor que se ha demostrado que conduce a la inestabilidad cromosómica en tumores colorrectales cuando se pierde. Ver Rajagopalan, H. et al. (2004) Nature 428:77-81. Se ha descubierto que el dominio WD40, que es importante en la interacción entre FBXW7 y ciclina E (ver Orlicky, S. et al. (2003) Cell 112:243-256), está mutado en el cáncer colorrectal. Ver Rajagopalan, supra. Se secuenció FBXW7 en 61 tumores NSCLC adicionales, pero no se identificaron mutaciones adicionales. Según el conocimiento de los inventores, no se han descrito mutaciones en FBXW7 previamente en NSCLC. [0144] It should be noted that the MRD identified three somatic mutations in the WD40 domain of the FBXW7 gene (see Variation ID No. 10007, 10008, and 10009). It is known that FBXW7 is a tumor suppressor that has been shown to lead to chromosomal instability in colorectal tumors when it is lost. See Rajagopalan, H. et al. (2004) Nature 428: 77-81. It has been found that the WD40 domain, which is important in the interaction between FBXW7 and cyclin E (see Orlicky, S. et al. (2003) Cell 112: 243-256), is mutated in colorectal cancer. See Rajagopalan, supra. FBXW7 was sequenced in 61 additional NSCLC tumors, but no additional mutations were identified. According to the inventors' knowledge, no mutations in FBXW7 have been previously described in NSCLC.

B. Identificación de variaciones mediante secuenciación Sanger B. Variation identification by Sanger sequencing

[0145] También se utilizó la secuenciación Sanger para identificar las variaciones de nucleótido en 52 de los 100 genes seleccionados originariamente. Específicamente, se utilizó la PCR para amplificar exones en aquellos genes de ADN genómico de tumor. Se secuenciaron los amplicones utilizando secuenciación Sanger estándar, y se compararon las secuencias con las secuencias de tipo salvaje correspondientes para identificar variaciones. Se compararon las variaciones con polimorfismos de nucleótido único en la base de datos “dbSNP” de NCBI (ver Sherry et al. (1999) Genome Res. 9:677-679) y con mutaciones somáticas en la base de datos del Catálogo de Mutaciones Somáticas en el Cáncer (COSMIC) (ver Bamford et al. (2004) British Journal of Cancer 91:355-358) para identificar las variaciones que no estaban presentes en estas bases de datos y de ese modo se determinó que eran nuevas. Se validaron las variaciones (es decir, se confirmaron) mediante la reamplificación y la resecuenciación de los exones a partir de las muestras de tumor originales. Se utilizó el ADN genómico de muestras normales apareadas del paciente para determinar si las variaciones eran mutaciones somáticas o polimorfismos de la línea germinal. En la Figura 3 se muestran los resultados del análisis anterior, incluyendo una lista de las variaciones de nucleótidos identificadas de ese modo. La Figura 3 se describe en mayor detalle en la Descripción Detallada de las Realizaciones anterior. También se identificaron mediante MRD algunas de las variaciones identificadas en la Figura 3 pero se omitieron de la Figura 1 (que indica las mutaciones identificadas mediante MRD) para evitar la redundancia. [0145] Sanger sequencing was also used to identify nucleotide variations in 52 of the 100 originally selected genes. Specifically, PCR was used to amplify exons in those tumor genomic DNA genes. Amplicons were sequenced using standard Sanger sequencing, and the sequences were compared with the corresponding wild-type sequences to identify variations. Variations were compared with single nucleotide polymorphisms in the NCBI “dbSNP” database (see Sherry et al. (1999) Genome Res. 9: 677-679) and with somatic mutations in the Mutation Catalog database Somatic in Cancer (COSMIC) (see Bamford et al. (2004) British Journal of Cancer 91: 355-358) to identify variations that were not present in these databases and thereby determined that they were new. Variations were validated (i.e. confirmed) by reamplification and resequencing of exons from the original tumor samples. Genomic DNA from normal paired samples from the patient was used to determine if the variations were somatic mutations or germline polymorphisms. The results of the previous analysis are shown in Figure 3, including a list of the nucleotide variations identified in this way. Figure 3 is described in greater detail in the Detailed Description of the previous Embodiments. Some of the variations identified in Figure 3 were also identified by MRD but were omitted from Figure 1 (indicating mutations identified by MRD) to avoid redundancy.

[0146] Aunque la invención anterior se ha descrito con más detalle a modo de ilustración y ejemplo para fines de claridad del entendimiento, las descripciones y ejemplos no deben interpretarse como limitantes del alcance de la invención. [0146] Although the above invention has been described in more detail by way of illustration and example for purposes of clarity of understanding, the descriptions and examples should not be construed as limiting the scope of the invention.

Listado de secuencias Sequence listing

[0147] [0147]

<110> Genentech, Inc. Kan, Zhengyan Peter s, Brock Seshagiri, Sorrasekar <110> Genentech, Inc. Kan, Zhengyan Peter s, Brock Seshagiri, Sorrasekar

<120> VARIACIONES GENÉTICAS ASOCIADAS CON TUMORES <120> GENETIC VARIATIONS ASSOCIATED WITH TUMORS

<130> P4007R1 <130> P4007R1

<141> 2007-11-15 <141> 2007-11-15

<150> US 60/ 866, 103 <150> US 60/866, 103

<151> 2006-11-16 <151> 2006-11-16

<150> US 60/ 948, 818 <150> US 60/948, 818

<151> 2007-07-10 <151> 2007-07-10

<160> 79 <160> 79

<210> 1 <210> 1

<211> 5766 <211> 5766

<212> ADN <212> DNA

<213> Homo sapiens <213> Homo sapiens

<400> 1 <400> 1

ggccttcccc ctgcgaggat cgccattggc ccgggttggc tttggaaagc 50 ggccttcccc ctgcgaggat cgccattggc ccgggttggc tttggaaagc 50

ggcggtggct ttgggccggg ctcggcctcg ggaacgccag gggcccctgg 100 ggcggtggct ttgggccggg ctcggcctcg ggaacgccag gggcccctgg 100

gtgcggacgg gcgcggccag gagggggtta aggcgcaggc ggcggcgggg 150 gtgcggacgg gcgcggccag gagggggtta aggcgcaggc ggcggcgggg 150

cgggggcggg cctggcgggc gccctctccg ggccctttgt taacaggcgc 200 cgggggcggg cctggcgggc gccctctccg ggccctttgt taacaggcgc 200

gtcccggcca ggcggagacg cggccgcggc catgggcggg cgcgggcgcg 250 gtcccggcca ggcggagacg cggccgcggc catgggcggg cgcgggcgcg 250

cggggcggcg gtgagggcgg ctggcggggc cgggggcgcc gggggggcgc 300 cggggcggcg gtgagggcgg ctggcggggc cgggggcgcc gggggggcgc 300

gcgggccgag ccgggcctga gccgggcccg cggaccgagc tgggagaggg 350 gcgggccgag ccgggcctga gccgggcccg cggaccgagc tgggagaggg 350

gttccggccc ccgacgtgct ggcgcgggaa aatgttggag atctgcctga 400 gttccggccc ccgacgtgct ggcgcgggaa aatgttggag atctgcctga 400

agctggtggg ctgcaaatcc aagaaggggc tgtcctcgtc ctccagctgt 450 agctggtggg ctgcaaatcc aagaaggggc tgtcctcgtc ctccagctgt 450

tatctggaag aagcccttca gcggccagta gcatctgact ttgagcctca 500 tatctggaag aagcccttca gcggccagta gcatctgact ttgagcctca 500

gggtctgagt gaagccgctc gttggaactc caaggaaaac cttctcgctg 550 gggtctgagt gaagccgctc gttggaactc caaggaaaac cttctcgctg 550

gacccagtga aaatgacccc aaccttttcg ttgcactgta tgattttgtg 600 gacccagtga aaatgacccc aaccttttcg ttgcactgta tgattttgtg 600

gccagtggag ataacactct aagcataact aaaggtgaaa agctccgggt 650 gccagtggag ataacactct aagcataact aaaggtgaaa agctccgggt 650

cttaggctat aatcacaatg gggaatggtg tgaagcccaa accaaaaatg 700 cttaggctat aatcacaatg gggaatggtg tgaagcccaa accaaaaatg 700

gccaaggctg ggtcccaagc aactacatca cgccagtcaa cagtctggag 750 gccaaggctg ggtcccaagc aactacatca cgccagtcaa cagtctggag 750

aaacactcct ggtaccatgg gcctgtgtcc cgcaatgccg ctgagtatct 800 aaacactcct ggtaccatgg gcctgtgtcc cgcaatgccg ctgagtatct 800

gctgagcagc gggatcaatg gcagcttctt ggtgcgtgag agtgagagca 850 gctgagcagc gggatcaatg gcagcttctt ggtgcgtgag agtgagagca 850

gtcctggcca gaggtccatc tcgctgagat acgaagggag ggtgtaccat 900 gtcctggcca gaggtccatc tcgctgagat acgaagggag ggtgtaccat 900

tacaggatca acactgcttc tgatggcaag ctctacgtct cctccgagag 950 tacaggatca acactgcttc tgatggcaag ctctacgtct cctccgagag 950

ccgcttcaac accctggccg agttggttca tcatcattca acggtggccg 1000 ccgcttcaac accctggccg agttggttca tcatcattca acggtggccg 1000

acgggctcat caccacgctc cattatccag ccccaaagcg caacaagccc 1050 acgggctcat caccacgctc cattatccag ccccaaagcg caacaagccc 1050

actgtctatg gtgtgtcccc caactacgac aagtgggaga tggaacgcac 1100 ggacatcacc atgaagcaca agctgggcgg gggccagtac ggggaggtgt 1150 acgagggcgt gtggaagaaa tacagcctga cggtggccgt gaagaccttg 1200 aaggaggaca ccatggaggt ggaagagttc ttgaaagaag ctgcagtcat 1250 gaaagagatc aaacacccta acctggtgca gctccttggg gtctgcaccc 1300 gggagccccc gttctatatc atcactgagt tcatgaccta cgggaacctc 1350 ctggactacc tgagggagtg caaccggcag gaggtgaacg ccgtggtgct 1400 gctgtacatg gccactcaga tctcgtcagc catggagtac ctggagaaga 1450 aaaacttcat ccacagagat cttgctgccc gaaactgcct ggtaggggag 1500 aaccacttgg tgaaggtagc tgattttggc ctgagcaggt tgatgacagg 1550 ggacacctac acagcccatg ctggagccaa gttccccatc aaatggactg 1600 cacccgagag cctggcctac aacaagttct ccatcaagtc cgacgtctgg 1650 gcatttggag tattgctttg ggaaattgct acctatggca tgtcccctta 1700 cccgggaatt gacctgtccc aggtgtatga gctgctagag aaggactacc 1750 gcatggagcg cccagaaggc tgcccagaga aggtctatga actcatgcga 1800 gcatgttggc agtggaatcc ctctgaccgg ccctcctttg ctgaaatcca 1850 ccaagccttt gaaacaatgt tccaggaatc cagtatctca gacgaagtgg 1900 aaaaggagct ggggaaacaa ggcgtccgtg gggctgtgag taccttgctg 1950 caggccccag agctgcccac caagacgagg acctccagga gagctgcaga 2000 gcacagagac accactgacg tgcctgagat gcctcactcc aagggccagg 2050 gagagagcga tcctctggac catgagcctg ccgtgtctcc attgctccct 2100 cgaaaagagc gaggtccccc ggagggcggc ctgaatgaag atgagcgcct 2150 tctccccaaa gacaaaaaga ccaacttgtt cagcgccttg atcaagaaga 2200 agaagaagac agccccaacc cctcccaaac gcagcagctc cttccgggag 2250 atggacggcc agccggagcg cagaggggcc ggcgaggaag agggccgaga 2300 catcagcaac ggggcactgg ctttcacccc cttggacaca gctgacccag 2350 ccaagtcccc aaagcccagc aatggggctg gggtccccaa tggagccctc 2400 cgggagtccg ggggctcagg cttccggtct ccccacctgt ggaagaagtc 2450 cagcacgctg accagcagcc gcctagccac cggcgaggag gagggcggtg 2500 gcagctccag caagcgcttc ctgcgctctt gctccgcctc ctgcgttccc 2550 catggggcca aggacacgga gtggaggtca gtcacgctgc ctcgggactt 2600 gcagtccacg ggaagacagt ttgactcgtc cacatttgga gggcacaaaa 2650 gtgagaagcc ggctctgcct cggaagaggg caggggagaa caggtctgac 2700 caggtgaccc gaggcacagt aacgcctccc cccaggctgg tgaaaaagaa 2750 tgaggaagct gctgatgagg tcttcaaaga catcatggag tccagcccgg 2800 gctccagccc gcccaacctg actccaaaac ccctccggcg gcaggtcacc 2850 gtggcccctg cctcgggcct cccccacaag gaagaagctg gaaagggcag 2900 tgccttaggg acccctgctg cagctgagcc agtgaccccc accagcaaag 2950 caggctcagg tgcaccaggg ggcaccagca agggccccgc cgaggagtcc 3000 agagtgagga ggcacaagca ctcctctgag tcgccaggga gggacaaggg 3050 gaaattgtcc aggctcaaac ctgccccgcc gcccccacca gcagcctctg 3100 cagggaaggc tggaggaaag ccctcgcaga gcccgagcca ggaggcggcc 3150 ggggaggcag tcctgggcgc aaagacaaaa gccacgagtc tggttgatgc 3200 tgtgaacagt gacgctgcca agcccagcca gccgggagag ggcctcaaaa 3250 agcccgtgct cccggccact ccaaagccac agtccgccaa gccgtcgggg 3300 acccccatca gcccagcccc cgttccctcc acgttgccat cagcatcctc 3350 ggccctggca ggggaccagc cgtcttccac cgccttcatc cctctcatat 3400 caacccgagt gtctcttcgg aaaacccgcc agcctccaga gcggatcgcc 3450 agcggcgcca tcaccaaggg cgtggtcctg gacagcaccg aggcgctgtg 3500 cctcgccatc tctaggaact ccgagcagat ggccagccac agcgcagtgc 3550 tggaggccgg caaaaacctc tacacgttct gcgtgagcta tgtggattcc 3600 atccagcaaa tgaggaacaa gtttgccttc cgagaggcca tcaacaaact 3650 ggagaataat ctccgggagc ttcagatctg cccggcgaca gcaggcagtg 3700 gtccagcggc cactcaggac ttcagcaagc tcctcagttc ggtgaaggaa 3750 atcagtgaca tagtgcagag gtagcagcag tcaggggtca ggtgtcaggc 3800 ccgtcggagc tgcctgcagc acatgcgggc tcgcccatac ccgtgacagt 3850 ggctgacaag ggactagtga gtcagcacct tggcccagga gctctgcgcc 3900 aggcagagct gagggccctg tggagtccag ctctactacc tacgtttgca 3950 ccgcctgccc tcccgcacct tcctcctccc cgctccgtct ctgtcctcga 4000 attttatctg tggagttcct gctccgtgga ctgcagtcgg catgccagga 4050 cccgccagcc ccgctcccac ctagtgcccc agactgagct ctccaggcca 4100 ggtgggaacg gctgatgtgg actgtctttt tcattttttt ctctctggag 4150 cccctcctcc cccggctggg cctccttctt ccacttctcc aagaatggaa 4200 gcctgaactg aggccttgtg tgtcaggccc tctgcctgca ctccctggcc 4250 ttgcccgtcg tgtgctgaag acatgtttca agaaccgcat ttcgggaagg 4300 gcatgcacgg gcatgcacac ggctggtcac tctgccctct gctgctgccc 4350 ggggtggggt gcactcgcca tttcctcacg tgcaggacag ctcttgattt 4400 gggtggaaaa cagggtgcta aagccaacca gcctttgggt cctgggcagg 4450 tgggagctga aaaggatcga ggcatggggc atgtcctttc catctgtcca 4500 catccccaga gcccagctct tgctctcttg tgacgtgcac tgtgaatcct 4550 ggcaagaaag cttgagtctc aagggtggca ggtcactgtc actgccgaca 4600 tccctccccc agcagaatgg aggcagggga caagggaggc agtggctagt 4650 ggggtgaaca gctggtgcca aatagcccca gactgggccc aggcaggtct 4700 gcaagggccc agagtgaacc gtcctttcac acatctgggt gccctgaaag 4750 ggcccttccc ctcccccact cctctaagac aaagtagatt cttacaaggc 4800 cctttccttt ggaacaagac agccttcact tttctgagtt cttgaagcat 4850 ttcaaagccc tgcctctgtg tagccgccct gagagagaat agagctgcca 4900 ctgggcacct gcgcacaggt gggaggaaag ggcctggcca gtcctggtcc 4950 tggctgcact cttgaactgg gcgaatgtct tatttaatta ccgtgagtga 5000 catagcctca tgttctgtgg gggtcatcag ggagggttag gaaaaccaca 5050 aacggagccc ctgaaagcct cacgtatttc acagagcacg cctgccatct 5100 tctccccgag gctgccccag gccggagccc agatacgggg gctgtgactc 5150 tgggcaggga cccggggtct cctggacctt gacagagcag ctaactccga 5200 gagcagtggg caggtggccg cccctgaggc ttcacgccgg gagaagccac 5250 cttcccaccc cttcataccg cctcgtgcca gcagcctcgc acaggcccta 5300 gctttacgct catcacctaa acttgtactt tatttttctg atagaaatgg 5350 tttcctctgg atcgttttat gcggttctta cagcacatca cctctttgcc 5400 cccgacggct gtgacgcagc cggagggagg cactagtcac cgacagcggc 5450 cttgaagaca gagcaaagcg cccacccagg tcccccgact gcctgtctcc 5500 atgaggtact ggtcccttcc ttttgttaac gtgatgtgcc actatatttt 5550 acacgtatct cttggtatgc atcttttata gacgctcttt tctaagtggc 5600 gtgtgcatag cgtcctgccc tgccccctcg ggggcctgtg gtggctcccc 5650 ctctgcttct cggggtccag tgcattttgt ttctgtatat gattctctgt 5700 ggtttttttt gaatccaaat ctgtcctctg tagtattttt taaataaatc 5750 agtgtttaca ttagaa 5766 actgtctatg gtgtgtcccc caactacgac aagtgggaga tggaacgcac 1100 ggacatcacc atgaagcaca agctgggcgg gggccagtac ggggaggtgt 1150 acgagggcgt gtggaagaaa tacagcctga cggtggccgt gaagaccttg 1200 aaggaggaca ccatggaggt ggaagagttc ttgaaagaag ctgcagtcat 1250 aaacacccta gaaagagatc acctggtgca gctccttggg gtctgcaccc 1300 gggagccccc gttctatatc atcactgagt tcatgaccta cgggaacctc 1350 ctggactacc tgagggagtg caaccggcag gaggtgaacg ccgtggtgct 1400 gctgtacatg gccactcaga tctcgtcagc catggagtac ctggagaaga 1450 aaaacttcat ccacagagat cttgctgccc gaaactgcct ggtaggggag 1500 aaccacttgg tgaaggtagc tgattttggc ctgagcaggt tgatgacagg 1550 ggacacctac acagcccatg ctggagccaa gttccccatc aaatggactg 1600 cacccgagag cctggcctac aacaagttct ccatcaagtc cgacgtctgg 1650 gcatttggag tattgctttg ggaaattgct acctatggca tgtcccctta 1700 cccgggaatt gacctgtccc aggtgtatga gctgctagag aaggactacc 1750 gcatggagcg cccagaaggc aggtctatga tgcccagaga actcatgcga 1800 gcatgttggc agtggaatcc ctctgaccgg ccctcctttg ctgaaatcca 1850 ccaagccttt gaaacaatgt tc caggaatc cagtatctca gacgaagtgg 1900 aaaaggagct ggggaaacaa ggcgtccgtg gggctgtgag taccttgctg 1950 caggccccag agctgcccac caagacgagg gagctgcaga acctccagga 2000 gcacagagac accactgacg tgcctgagat gcctcactcc aagggccagg 2050 gagagagcga tcctctggac catgagcctg ccgtgtctcc attgctccct 2100 cgaaaagagc gaggtccccc ggagggcggc ctgaatgaag atgagcgcct 2150 tctccccaaa gacaaaaaga ccaacttgtt cagcgccttg atcaagaaga 2200 agaagaagac agccccaacc cctcccaaac gcagcagctc cttccgggag 2250 atggacggcc agccggagcg cagaggggcc ggcgaggaag agggccgaga 2300 catcagcaac ggggcactgg ctttcacccc cttggacaca gctgacccag 2350 ccaagtcccc aaagcccagc aatggggctg gggtccccaa tggagccctc 2400 cgggagtccg ggggctcagg cttccggtct ccccacctgt ggaagaagtc 2450 cagcacgctg accagcagcc gcctagccac cggcgaggag gagggcggtg 2500 gcagctccag caagcgcttc ctgcgctctt gctccgcctc ctgcgttccc 2550 aggacacgga catggggcca gtggaggtca gtcacgctgc ctcgggactt 2600 gcagtccacg ggaagacagt ttgactcgtc gggcacaaaa cacatttgga 2650 gtgagaagcc ggctctgcct cggaagaggg caggggagaa CAGG tctgac 2700 caggtgaccc gaggcacagt aacgcctccc cccaggctgg tgaaaaagaa 2750 tgaggaagct gctgatgagg tcttcaaaga catcatggag tccagcccgg 2800 gctccagccc gcccaacctg actccaaaac ccctccggcg gcaggtcacc 2850 gtggcccctg cctcgggcct cccccacaag gaagaagctg gaaagggcag 2900 tgccttaggg acccctgctg cagctgagcc agtgaccccc accagcaaag 2950 caggctcagg tgcaccaggg ggcaccagca agggccccgc cgaggagtcc 3000 ggcacaagca agagtgagga ctcctctgag tcgccaggga gggacaaggg 3050 gaaattgtcc aggctcaaac ctgccccgcc gcccccacca gcagcctctg 3100 cagggaaggc tggaggaaag gcccgagcca ccctcgcaga ggaggcggcc 3150 ggggaggcag tcctgggcgc aaagacaaaa gccacgagtc tggttgatgc 3200 gacgctgcca tgtgaacagt agcccagcca gccgggagag ggcctcaaaa 3250 agcccgtgct cccggccact ccaaagccac agtccgccaa gccgtcgggg 3300 acccccatca gcccagcccc cgttccctcc acgttgccat cagcatcctc 3350 ggccctggca ggggaccagc cgtcttccac cgccttcatc cctctcatat 3400 caacccgagt gtctcttcgg aaaacccgcc agcctccaga gcggatcgcc 3450 agcggcgcca tcaccaaggg cgtggtcctg gacagcaccg aggcgctgtg 3500 cctcgccatc t ctaggaact ccgagcagat ggccagccac agcgcagtgc 3550 tggaggccgg caaaaacctc tacacgttct gcgtgagcta tgtggattcc 3600 tgaggaacaa atccagcaaa cgagaggcca gtttgccttc tcaacaaact 3650 ggagaataat ctccgggagc ttcagatctg cccggcgaca gcaggcagtg 3700 gtccagcggc cactcaggac ttcagcaagc tcctcagttc ggtgaaggaa 3750 atcagtgaca tagtgcagag gtagcagcag tcaggggtca ggtgtcaggc 3800 ccgtcggagc tgcctgcagc acatgcgggc tcgcccatac ccgtgacagt 3850 ggctgacaag ggactagtga gtcagcacct tggcccagga gctctgcgcc 3900 aggcagagct gagggccctg tggagtccag ctctactacc tacgtttgca 3950 ccgcctgccc tcccgcacct tcctcctccc cgctccgtct ctgtcctcga 4000 attttatctg tggagttcct gctccgtgga ctgcagtcgg catgccagga 4050 cccgccagcc ccgctcccac ctagtgcccc agactgagct ctccaggcca 4100 ggtgggaacg gctgatgtgg actgtctttt tcattttttt ctctctggag 4150 cccctcctcc cccggctggg cctccttctt ccacttctcc aagaatggaa 4200 gcctgaactg aggccttgtg tgtcaggccc tctgcctgca ctccctggcc 4250 ttgcccgtcg tgtgctgaag acatgtttca agaaccgcat ttcgggaagg 4300 gcatgcacgg gcatgcacac ggctggtcac GTCT ccctct gctgctgccc 4350 ggggtggggt gcactcgcca tttcctcacg tgcaggacag ctcttgattt 4400 cagggtgcta gggtggaaaa aagccaacca gcctttgggt cctgggcagg 4450 aaaggatcga tgggagctga atgtcctttc ggcatggggc catctgtcca 4500 catccccaga gcccagctct tgctctcttg tgacgtgcac tgtgaatcct 4550 ggcaagaaag cttgagtctc aagggtggca actgccgaca ggtcactgtc 4600 tccctccccc agcagaatgg aggcagggga caagggaggc agtggctagt 4650 gctggtgcca ggggtgaaca aatagcccca gactgggccc aggcaggtct 4700 gcaagggccc agagtgaacc gtcctttcac acatctgggt gccctgaaag 4750 ggcccttccc ctcccccact cctctaagac aaagtagatt cttacaaggc 4800 cctttccttt ggaacaagac agccttcact tttctgagtt cttgaagcat 4850 ttcaaagccc tgcctctgtg tagccgccct gagagagaat agagctgcca ctgggcacct 4900 gcgcacaggt gggaggaaag ggcctggcca gtcctggtcc tggctgcact 4950 cttgaactgg gcgaatgtct tatttaatta ccgtgagtga 5000 catagcctca tgttctgtgg gggtcatcag ggagggttag gaaaaccaca 5050 aacggagccc ctgaaagcct cacgtatttc acagagcacg cctgccatct 5100 tctccccgag gctgccccag gccggagccc agatacgggg gctgtgactc 5150 tgggcaggga cccggggtct cctggacctt gacagagcag ctaactccga 5200 gagcagtggg caggtggccg cccctgaggc ttcacgccgg gagaagccac 5250 cttcccaccc cttcataccg cctcgtgcca gcagcctcgc acaggcccta 5300 gctttacgct catcacctaa acttgtactt tatttttctg atagaaatgg 5350 tttcctctgg atcgttttat gcggttctta cagcacatca cctctttgcc 5400 cccgacggct gtgacgcagc cggagggagg cactagtcac cgacagcggc 5450 cttgaagaca gagcaaagcg cccacccagg tcccccgact gcctgtctcc 5500 atgaggtact ggtcccttcc ttttgttaac gtgatgtgcc actatatttt 5550 acacgtatct cttggtatgc atcttttata gacgctcttt tctaagtggc 5600 gtgtgcatag cgtcctgccc tgccccctcg ggggcctgtg gtggctcccc 5650 ctctgcttct cggggtccag tgcattttgt ttctgtatat gattctctgt 5700 ggtttttttt gaatccaaat ctgtcctctg tagtattttt taaataaatc ttagaa agtgtttaca 5750 5766

<210> 2 <210> 2

<211> 10701 <211> 10701

<212> ADN <212> DNA

<213> Homo sapiens <213> Homo sapiens

<400> 2 <400> 2

tggagacaga atggaggtgc tgccggactc ggaaatgggg tccaagggta 50 tggagacaga atggaggtgc tgccggactc ggaaatgggg tccaagggta 50

gccaaggatg gctgcagctt catatgatca gttgttaaag caagttgagg 100 gccaaggatg gctgcagctt catatgatca gttgttaaag caagttgagg 100

cactgaagat ggagaactca aatcttcgac aagagctaga agataattcc 150 cactgaagat ggagaactca aatcttcgac aagagctaga agataattcc 150

aatcatctta caaaactgga aactgaggca tctaatatga aggaagtact 200 aatcatctta caaaactgga aactgaggca tctaatatga aggaagtact 200

taaacaacta caaggaagta ttgaagatga agctatggct tcttctggac 250 agattgattt attagagcgt cttaaagagc ttaacttaga tagcagtaat 300 ttccctggag taaaactgcg gtcaaaaatg tccctccgtt cttatggaag 350 ccgggaagga tctgtatcaa gccgttctgg agagtgcagt cctgttccta 400 tgggttcatt tccaagaaga gggtttgtaa atggaagcag agaaagtact 450 ggatatttag aagaacttga gaaagagagg tcattgcttc ttgctgatct 500 tgacaaagaa gaaaaggaaa aagactggta ttacgctcaa cttcagaatc 550 tcactaaaag aatagatagt cttcctttaa ctgaaaattt ttccttacaa 600 acagatatga ccagaaggca attggaatat gaagcaaggc aaatcagagt 650 tgcgatggaa gaacaactag gtacctgcca ggatatggaa aaacgagcac 700 agcgaagaat agccagaatt cagcaaatcg aaaaggacat acttcgtata 750 cgacagcttt tacagtccca agcaacagaa gcagagaggt catctcagaa 800 caagcatgaa accggctcac atgatgctga gcggcagaat gaaggtcaag 850 gagtgggaga aatcaacatg gcaacttctg gtaatggtca gggttcaact 900 acacgaatgg accatgaaac agccagtgtt ttgagttcta gtagcacaca 950 ctctgcacct cgaaggctga caagtcatct gggaaccaag gtggaaatgg 1000 tgtattcatt gttgtcaatg cttggtactc atgataagga tgatatgtcg 1050 cgaactttgc tagctatgtc tagctcccaa gacagctgta tatccatgcg 1100 acagtctgga tgtcttcctc tcctcatcca gcttttacat ggcaatgaca 1150 aagactctgt attgttggga aattcccggg gcagtaaaga ggctcgggcc 1200 agggccagtg cagcactcca caacatcatt cactcacagc ctgatgacaa 1250 gagaggcagg cgtgaaatcc gagtccttca tcttttggaa cagatacgcg 1300 cttactgtga aacctgttgg gagtggcagg aagctcatga accaggcatg 1350 gaccaggaca aaaatccaat gccagctcct gttgaacatc agatctgtcc 1400 tgctgtgtgt gttctaatga aactttcatt tgatgaagag catagacatg 1450 caatgaatga actaggggga ctacaggcca ttgcagaatt attgcaagtg 1500 gactgtgaaa tgtatgggct tactaatgac cactacagta ttacactaag 1550 acgatatgct ggaatggctt tgacaaactt gacttttgga gatgtagcca 1600 acaaggctac gctatgctct atgaaaggct gcatgagagc acttgtggcc 1650 caactaaaat ctgaaagtga agacttacag caggttattg cgagtgtttt 1700 gaggaatttg tcttggcgag cagatgtaaa tagtaaaaag acgttgcgag 1750 aagttggaag tgtgaaagca ttgatggaat gtgctttaga agttaaaaag 1800 gaatcaaccc tcaaaagcgt attgagtgcc ttatggaatt tgtcagcaca 1850 ttgcactgag aataaagctg atatatgtgc tgtagatggt gcacttgcat 1900 ttttggttgg cactcttact taccggagcc agacaaacac tttagccatt 1950 attgaaagtg gaggtgggat attacggaat gtgtccagct tgatagctac 2000 aaatgaggac cacaggcaaa tcctaagaga gaacaactgt ctacaaactt 2050 tattacaaca cttaaaatct catagtttga caatagtcag taatgcatgt 2100 ggaactttgt ggaatctctc agcaagaaat cctaaagacc aggaagcatt 2150 atgggacatg ggggcagtta gcatgctcaa gaacctcatt cattcaaagc 2200 acaaaatgat tgctatggga agtgctgcag ctttaaggaa tctcatggca 2250 aataggcctg cgaagtacaa ggatgccaat attatgtctc ctggctcaag 2300 cttgccatct cttcatgtta ggaaacaaaa agccctagaa gcagaattag 2350 atgctcagca cttatcagaa acttttgaca atatagacaa tttaagtccc 2400 aaggcatctc atcgtagtaa gcagagacac aagcaaagtc tctatggtga 2450 ttatgttttt gacaccaatc gacatgatga taataggtca gacaatttta 2500 atactggcaa catgactgtc ctttcaccat atttgaatac tacagtgtta 2550 cccagctcct cttcatcaag aggaagctta gatagttctc gttctgaaaa 2600 agatagaagt ttggagagag aacgcggaat tggtctaggc aactaccatc 2650 cagcaacaga aaatccagga acttcttcaa agcgaggttt gcagatctcc 2700 accactgcag cccagattgc caaagtcatg gaagaagtgt cagccattca 2750 tacctctcag gaagacagaa gttctgggtc taccactgaa ttacattgtg 2800 tgacagatga gagaaatgca cttagaagaa gctctgctgc ccatacacat 2850 tcaaacactt acaatttcac taagtcggaa aattcaaata ggacatgttc 2900 tatgccttat gccaaattag aatacaagag atcttcaaat gatagtttaa 2950 atagtgtcag tagtagtgat ggttatggta aaagaggtca aatgaaaccc 3000 tcgattgaat cctattctga agatgatgaa agtaagtttt gcagttatgg 3050 tcaataccca gccgacctag cccataaaat acatagtgca aatcatatgg 3100 atgataatga tggagaacta gatacaccaa taaattatag tcttaaatat 3150 tcagatgagc agttgaactc tggaaggcaa agtccttcac agaatgaaag 3200 atgggcaaga cccaaacaca taatagaaga tgaaataaaa caaagtgagc 3250 aaagacaatc aaggaatcaa agtacaactt atcctgttta tactgagagc 3300 actgatgata aacacctcaa gttccaacca cattttggac agcaggaatg 3350 tgtttctcca tacaggtcac ggggagccaa tggttcagaa acaaatcgag 3400 tgggttctaa tcatggaatt aatcaaaatg taagccagtc tttgtgtcaa 3450 gaagatgact atgaagatga taagcctacc aattatagtg aacgttactc 3500 tgaagaagaa cagcatgaag aagaagagag accaacaaat tatagcataa 3550 aatataatga agagaaacgt catgtggatc agcctattga ttatagttta 3600 aaatatgcca cagatattcc ttcatcacag aaacagtcat tttcattctc 3650 aaagagttca tctggacaaa gcagtaaaac cgaacatatg tcttcaagca 3700 gtgagaatac gtccacacct tcatctaatg ccaagaggca gaatcagctc 3750 catccaagtt ctgcacagag tagaagtggt cagcctcaaa aggctgccac 3800 ttgcaaagtt tcttctatta accaagaaac aatacagact tattgtgtag 3850 aagatactcc aatatgtttt tcaagatgta gttcattatc atctttgtca 3900 tcagctgaag atgaaatagg atgtaatcag acgacacagg aagcagattc 3950 tgctaatacc ctgcaaatag cagaaataaa agaaaagatt ggaactaggt 4000 cagctgaaga tcctgtgagc gaagttccag cagtgtcaca gcaccctaga 4050 accaaatcca gcagactgca gggttctagt ttatcttcag aatcagccag 4100 gcacaaagct gttgaatttt cttcaggagc gaaatctccc tccaaaagtg 4150 gtgctcagac acccaaaagt ccacctgaac actatgttca ggagacccca 4200 ctcatgttta gcagatgtac ttctgtcagt tcacttgata gttttgagag 4250 tcgttcgatt gccagctccg ttcagagtga accatgcagt ggaatggtaa 4300 gtggcattat aagccccagt gatcttccag atagccctgg acaaaccatg 4350 ccaccaagca gaagtaaaac acctccacca cctcctcaaa cagctcaaac 4400 caagcgagaa gtacctaaaa ataaagcacc tactgctgaa aagagagaga 4450 gtggacctaa gcaagctgca gtaaatgctg cagttcagag ggtccaggtt 4500 cttccagatg ctgatacttt attacatttt gccacggaaa gtactccaga 4550 tggattttct tgttcatcca gcctgagtgc tctgagcctc gatgagccat 4600 ttatacagaa agatgtggaa ttaagaataa tgcctccagt tcaggaaaat 4650 gacaatggga atgaaacaga atcagagcag cctaaagaat caaatgaaaa 4700 ccaagagaaa gaggcagaaa aaactattga ttctgaaaag gacctattag 4750 atgattcaga tgatgatgat attgaaatac tagaagaatg tattatttct 4800 gccatgccaa caaagtcatc acgtaaagca aaaaagccag cccagactgc 4850 ttcaaaatta cctccacctg tggcaaggaa accaagtcag ctgcctgtgt 4900 acaaacttct accatcacaa aacaggttgc aaccccaaaa gcatgttagt 4950 tttacaccgg gggatgatat gccacgggtg tattgtgttg aagggacacc 5000 tataaacttt tccacagcta catctctaag tgatctaaca atcgaatccc 5050 ctccaaatga gttagctgct ggagaaggag ttagaggagg ggcacagtca 5100 ggtgaatttg aaaaacgaga taccattcct acagaaggca gaagtacaga 5150 tgaggctcaa ggaggaaaaa cctcatctgt aaccatacct gaattggatg 5200 acaataaagc agaggaaggt gatattcttg cagaatgcat taattctgct 5250 atgcccaaag ggaaaagtca caagcctttc cgtgtgaaaa agataatgga 5300 ccaggtccag caagcatctg cgtcttcttc tgcacccaac aaaaatcagt 5350 tagatggtaa gaaaaagaaa ccaacttcac cagtaaaacc tataccacaa 5400 aatactgaat ataggacacg tgtaagaaaa aatgcagact caaaaaataa 5450 tttaaatgct gagagagttt tctcagacaa caaagattca aagaaacaga 5500 atttgaaaaa taattccaag gtcttcaatg ataagctccc aaataatgaa 5550 gatagagtca gaggaagttt tgcttttgat tcacctcatc attacacgcc 5600 tattgaagga actccttact gtttttcacg aaatgattct ttgagttctc 5650 tagattttga tgatgatgat gttgaccttt ccagggaaaa ggctgaatta 5700 agaaaggcaa aagaaaataa ggaatcagag gctaaagtta ccagccacac 5750 agaactaacc tccaaccaac aatcagctaa taagacacaa gctattgcaa 5800 agcagccaat aaatcgaggt cagcctaaac ccatacttca gaaacaatcc 5850 acttttcccc agtcatccaa agacatacca gacagagggg cagcaactga 5900 tgaaaagtta cagaattttg ctattgaaaa tactccggtt tgcttttctc 5950 ataattcctc tctgagttct ctcagtgaca ttgaccaaga aaacaacaat 6000 aaagaaaatg aacctatcaa agagactgag ccccctgact cacagggaga 6050 accaagtaaa cctcaagcat caggctatgc tcctaaatca tttcatgttg 6100 aagatacccc agtttgtttc tcaagaaaca gttctctcag ttctcttagt 6150 attgactctg aagatgacct gttgcaggaa tgtataagct ccgcaatgcc 6200 aaaaaagaaa aagccttcaa gactcaaggg tgataatgaa aaacatagtc 6250 ccagaaatat gggtggcata ttaggtgaag atctgacact tgatttgaaa 6300 gatatacaga gaccagattc agaacatggt ctatcccctg attcagaaaa 6350 ttttgattgg aaagctattc aggaaggtgc aaattccata gtaagtagtt 6400 tacatcaagc tgctgctgct gcatgtttat ctagacaagc ttcgtctgat 6450 tcagattcca tcctttccct gaaatcagga atctctctgg gatcaccatt 6500 tcatcttaca cctgatcaag aagaaaaacc ctttacaagt aataaaggcc 6550 cacgaattct aaaaccaggg gagaaaagta cattggaaac taaaaagata 6600 gaatctgaaa gtaaaggaat caaaggagga aaaaaagttt ataaaagttt 6650 gattactgga aaagttcgat ctaattcaga aatttcaggc caaatgaaac 6700 agccccttca agcaaacatg ccttcaatct ctcgaggcag gacaatgatt 6750 catattccag gagttcgaaa tagctcctca agtacaagtc ctgtttctaa 6800 aaaaggccca ccccttaaga ctccagcctc caaaagccct agtgaaggtc 6850 aaacagccac cacttctcct agaggagcca agccatctgt gaaatcagaa 6900 ttaagccctg ttgccaggca gacatcccaa ataggtgggt caagtaaagc 6950 accttctaga tcaggatcta gagattcgac cccttcaaga cctgcccagc 7000 aaccattaag tagacctata cagtctcctg gccgaaactc aatttcccct 7050 ggtagaaatg gaataagtcc tcctaacaaa ttatctcaac ttccaaggac 7100 atcatcccct agtactgctt caactaagtc ctcaggttct ggaaaaatgt 7150 catatacatc tccaggtaga cagatgagcc aacagaacct taccaaacaa 7200 acaggtttat ccaagaatgc cagtagtatt ccaagaagtg agtctgcctc 7250 caaaggacta aatcagatga ataatggtaa tggagccaat aaaaaggtag 7300 aactttctag aatgtcttca actaaatcaa gtggaagtga atctgataga 7350 tcagaaagac ctgtattagt acgccagtca actttcatca aagaagctcc 7400 aagcccaacc ttaagaagaa aattggagga atctgcttca tttgaatctc 7450 tttctccatc atctagacca gcttctccca ctaggtccca ggcacaaact 7500 ccagttttaa gtccttccct tcctgatatg tctctatcca cacattcgtc 7550 tgttcaggct ggtggatggc gaaaactccc acctaatctc agtcccacta 7600 tagagtataa tgatggaaga ccagcaaagc gccatgatat tgcacggtct 7650 cattctgaaa gtccttctag acttccaatc aataggtcag gaacctggaa 7700 acgtgagcac agcaaacatt catcatccct tcctcgagta agcacttgga 7750 gaagaactgg aagttcatct tcaattcttt ctgcttcatc agaatccagt 7800 gaaaaagcaa aaagtgagga tgaaaaacat gtgaactcta tttcaggaac 7850 caaacaaagt aaagaaaacc aagtatccgc aaaaggaaca tggagaaaaa 7900 taaaagaaaa tgaattttct cccacaaata gtacttctca gaccgtttcc 7950 tcaggtgcta caaatggtgc tgaatcaaag actctaattt atcaaatggc 8000 acctgctgtt tctaaaacag aggatgtttg ggtgagaatt gaggactgtc 8050 ccattaacaa tcctagatct ggaagatctc ccacaggtaa tactcccccg 8100 gtgattgaca gtgtttcaga aaaggcaaat ccaaacatta aagattcaaa 8150 agataatcag gcaaaacaaa atgtgggtaa tggcagtgtt cccatgcgta 8200 ccgtgggttt ggaaaatcgc ctgaactcct ttattcaggt ggatgcccct 8250 gaccaaaaag gaactgagat aaaaccagga caaaataatc ctgtccctgt 8300 atcagagact aatgaaagtt ctatagtgga acgtacccca ttcagttcta 8350 gcagctcaag caaacacagt tcacctagtg ggactgttgc tgccagagtg 8400 actcctttta attacaaccc aagccctagg aaaagcagcg cagatagcac 8450 ttcagctcgg ccatctcaga tcccaactcc agtgaataac aacacaaaga 8500 agcgagattc caaaactgac agcacagaat ccagtggaac ccaaagtcct 8550 aagcgccatt ctgggtctta ccttgtgaca tctgtttaaa agagaggaag 8600 aatgaaacta agaaaattct atgttaatta caactgctat atagacattt 8650 tgtttcaaat gaaactttaa aagactgaaa aattttgtaa ataggtttga 8700 ttcttgttag agggtttttg ttctggaagc catatttgat agtatacttt 8750 gtcttcactg gtcttatttt gggaggcact cttgatggtt aggaaaaaaa 8800 tagtaaagcc aagtatgttt gtacagtatg ttttacatgt atttaaagta 8850 gcatcccatc ccaacttcct ttaattattg cttgtcttaa aataatgaac 8900 actacagata gaaaatatga tatattgctg ttatcaatca tttctagatt 8950 ataaactgac taaacttaca tcagggaaaa attggtattt atgcaaaaaa 9000 aaatgttttt gtccttgtga gtccatctaa catcataatt aatcatgtgg 9050 ctgtgaaatt cacagtaata tggttcccga tgaacaagtt tacccagcct 9100 gctttgcttt actgcatgaa tgaaactgat ggttcaattt cagaagtaat 9150 gattaacagt tatgtggtca catgatgtgc atagagatag ctacagtgta 9200 ataatttaca ctattttgtg ctccaaacaa aacaaaaatc tgtgtaactg 9250 taaaacattg aatgaaacta ttttacctga actagatttt atctgaaagt 9300 aggtagaatt tttgctatgc tgtaatttgt tgtatattct ggtatttgag 9350 gtgagatggc tgctctttta ttaatgagac atgaattgtg tctcaacaga 9400 aactaaatga acatttcaga ataaattatt gctgtatgta aactgttact 9450 gaaattggta tttgtttgaa gggtcttgtt tcacatttgt attaataatt 9500 gtttaaaatg cctcttttaa aagcttatat aaattttttt cttcagcttc 9550 tatgcattaa gagtaaaatt cctcttactg taataaaaac aattgaagaa 9600 gactgttgcc acttaaccat tccatgcgtt ggcacttatc tattcctgaa 9650 atttctttta tgtgattagc tcatcttgat ttttaatatt tttccactta 9700 aacttttttt tcttactcca ctggagctca gtaaaagtaa attcatgtaa 9750 tagcaatgca agcagcctag cacagactaa gcattgagca taataggccc 9800 acataatttc ctctttctta atattataga attctgtact tgaaattgat 9850 tcttagacat tgcagtctct tcgaggcttt acagtgtaaa ctgtcttgcc 9900 ccttcatctt cttgttgcaa ctgggtctga catgaacact ttttatcacc 9950 ctgtatgtta gggcaagatc tcagcagtga agtataatca gcactttgcc 10000 atgctcagaa aattcaaatc acatggaact ttagaggtag atttaatacg 10050 attaagatat tcagaagtat attttagaat ccctgcctgt taaggaaact 10100 ttatttgtgg taggtacagt tctggggtac atgttaagtg tccccttata 10150 cagtggaggg aagtcttcct tcctgaagga aaataaactg acacttatta 10200 actaagataa tttacttaat atatcttccc tgatttgttt taaaagatca 10250 gagggtgact gatgatacat gcatacatat ttgttgaata aatgaaaatt 10300 tatttttagt gataagattc atacactctg tatttgggga gggaaaacct 10350 ttttaagcat ggtggggcac tcagatagga gtgaatacac ctacctggtg 10400 ccttgaaaat cacatcaagt agttaattat ctacccctta cctgtgttta 10450 taacttccag gtaatgagaa tgattttttt taaagctaaa atgccagtaa 10500 ataaaagtgc tatgacttga gctaagatat ttgactccaa tgcctgtact 10550 gtgtctactg caccactttg taaacacttc aatttactat ctttgaaatg 10600 attgaccttt aaatttttgc caaatgttat ctgaaattgt ctatgaatac 10650 catctacttc tgttgttttc ccaggcttcc ataaacaatg gagatacatg 10700 c 10701 taaacaacta ttgaagatga caaggaagta agctatggct tcttctggac 250 agattgattt attagagcgt cttaaagagc ttaacttaga tagcagtaat 300 ttccctggag taaaactgcg gtcaaaaatg tccctccgtt cttatggaag 350 tctgtatcaa ccgggaagga gccgttctgg agagtgcagt cctgttccta 400 tgggttcatt tccaagaaga gggtttgtaa atggaagcag agaaagtact 450 ggatatttag aagaacttga gaaagagagg tcattgcttc ttgctgatct 500 tgacaaagaa gaaaaggaaa ttacgctcaa aagactggta cttcagaatc 550 tcactaaaag aatagatagt cttcctttaa ctgaaaattt ttccttacaa 600 ccagaaggca acagatatga attggaatat gaagcaaggc aaatcagagt 650 gaacaactag tgcgatggaa ggatatggaa gtacctgcca aaacgagcac 700 agcgaagaat agccagaatt cagcaaatcg aaaaggacat acttcgtata 750 tacagtccca cgacagcttt agcaacagaa gcagagaggt catctcagaa 800 caagcatgaa accggctcac atgatgctga gcggcagaat gaaggtcaag 850 gagtgggaga aatcaacatg gcaacttctg gtaatggtca gggttcaact 900 acacgaatgg accatgaaac agccagtgtt gtagcacaca ttgagttcta 950 ctctgcacct cgaaggctga caagtcatct gggaaccaag gtggaaatgg 1000 tgtattcatt gttgtcaatg cttggtactc atgataa gga tgatatgtcg 1050 cgaactttgc tagctatgtc tagctcccaa gacagctgta tatccatgcg 1100 acagtctgga tgtcttcctc tcctcatcca gcttttacat ggcaatgaca 1150 aagactctgt attgttggga AATTCCCGGG gcagtaaaga ggctcgggcc 1200 cagcactcca agggccagtg cactcacagc caacatcatt ctgatgacaa 1250 gagaggcagg cgtgaaatcc gagtccttca tcttttggaa cagatacgcg 1300 cttactgtga aacctgttgg gagtggcagg aagctcatga accaggcatg 1350 gaccaggaca aaaatccaat gccagctcct gttgaacatc agatctgtcc 1400 tgctgtgtgt gttctaatga aactttcatt tgatgaagag catagacatg 1450 actaggggga caatgaatga ctacaggcca ttgcagaatt attgcaagtg 1500 gactgtgaaa tgtatgggct tactaatgac cactacagta ttacactaag 1550 acgatatgct ggaatggctt tgacaaactt gatgtagcca gacttttgga 1600 acaaggctac gctatgctct atgaaaggct gcatgagagc acttgtggcc 1650 caactaaaat ctgaaagtga agacttacag caggttattg cgagtgtttt 1700 gaggaatttg tcttggcgag cagatgtaaa tagtaaaaag acgttgcgag 1750 aagttggaag tgtgaaagca ttgatggaat gtgctttaga agttaaaaag 1800 gaatcaaccc tcaaaagcgt attgagtgcc ttatggaatt tgtcagcaca 1850 ttg cactgag aataaagctg atatatgtgc tgtagatggt gcacttgcat 1900 ttttggttgg cactcttact taccggagcc agacaaacac tttagccatt 1950 attgaaagtg gaggtgggat attacggaat gtgtccagct tgatagctac 2000 aaatgaggac cacaggcaaa tcctaagaga gaacaactgt ctacaaactt 2050 tattacaaca cttaaaatct catagtttga caatagtcag taatgcatgt 2100 ggaactttgt ggaatctctc agcaagaaat cctaaagacc aggaagcatt 2150 atgggacatg ggggcagtta gcatgctcaa gaacctcatt cattcaaagc 2200 acaaaatgat tgctatggga agtgctgcag tctcatggca ctttaaggaa 2250 aataggcctg cgaagtacaa ggatgccaat attatgtctc ctggctcaag 2300 cttcatgtta cttgccatct ggaaacaaaa agccctagaa gcagaattag 2350 cttatcagaa atgctcagca atatagacaa acttttgaca tttaagtccc 2400 atcgtagtaa aaggcatctc gcagagacac aagcaaagtc tctatggtga 2450 gacaccaatc ttatgttttt gacatgatga taataggtca gacaatttta 2500 atactggcaa catgactgtc ctttcaccat atttgaatac tacagtgtta 2550 cccagctcct cttcatcaag aggaagctta gatagttctc gttctgaaaa 2600 agatagaagt ttggagagag aacgcggaat tggtctaggc aactaccatc 2650 aaatccagga cagcaacaga ACTTC TTCAA agcgaggttt gcagatctcc 2700 accactgcag cccagattgc caaagtcatg gaagaagtgt cagccattca 2750 tacctctcag gaagacagaa gttctgggtc taccactgaa ttacattgtg 2800 gagaaatgca tgacagatga cttagaagaa gctctgctgc ccatacacat 2850 tcaaacactt acaatttcac taagtcggaa aattcaaata ggacatgttc 2900 tatgccttat gccaaattag aatacaagag atcttcaaat gatagtttaa 2950 atagtgtcag tagtagtgat ggttatggta aaagaggtca aatgaaaccc 3000 tcgattgaat cctattctga agatgatgaa agtaagtttt gcagttatgg 3050 tcaataccca gccgacctag cccataaaat acatagtgca aatcatatgg 3100 tggagaacta atgataatga gatacaccaa taaattatag tcttaaatat 3150 tcagatgagc agttgaactc tggaaggcaa agtccttcac agaatgaaag 3200 cccaaacaca atgggcaaga taatagaaga tgaaataaaa caaagtgagc 3250 aaagacaatc aaggaatcaa agtacaactt atcctgttta tactgagagc 3300 aacacctcaa actgatgata gttccaacca cattttggac agcaggaatg 3350 tgtttctcca tacaggtcac ggggagccaa tggttcagaa acaaatcgag 3400 tgggttctaa tcatggaatt aatcaaaatg taagccagtc tttgtgtcaa 3450 atgaagatga gaagatgact taagcctacc aattatagtg aacgtta ctc 3500 tgaagaagaa cagcatgaag aagaagagag accaacaaat tatagcataa 3550 aatataatga agagaaacgt catgtggatc agcctattga ttatagttta 3600 aaatatgcca cagatattcc ttcatcacag aaacagtcat tttcattctc 3650 tctggacaaa aaagagttca gcagtaaaac cgaacatatg tcttcaagca 3700 gtgagaatac gtccacacct tcatctaatg ccaagaggca gaatcagctc 3750 catccaagtt ctgcacagag tagaagtggt cagcctcaaa aggctgccac 3800 ttgcaaagtt tcttctatta accaagaaac aatacagact tattgtgtag 3850 aagatactcc aatatgtttt tcaagatgta atctttgtca gttcattatc 3900 tcagctgaag atgaaatagg atgtaatcag acgacacagg aagcagattc 3950 tgctaatacc ctgcaaatag cagaaataaa agaaaagatt ggaactaggt 4000 tcctgtgagc cagctgaaga cagtgtcaca gaagttccag gcaccctaga 4050 gcagactgca accaaatcca gggttctagt ttatcttcag aatcagccag 4100 gcacaaagct gttgaatttt cttcaggagc gaaatctccc tccaaaagtg 4150 gtgctcagac acccaaaagt ccacctgaac ggagacccca actatgttca 4200 ctcatgttta gcagatgtac ttctgtcagt tcacttgata gttttgagag 4250 tcgttcgatt gccagctccg ttcagagtga accatgcagt ggaatggtaa 4300 gtggcattat aag ccccagt gatcttccag atagccctgg acaaaccatg 4350 gaagtaaaac ccaccaagca acctccacca cctcctcaaa cagctcaaac 4400 gtacctaaaa caagcgagaa ataaagcacc tactgctgaa aagagagaga 4450 gcaagctgca gtggacctaa gtaaatgctg cagttcagag ggtccaggtt 4500 cttccagatg ctgatacttt attacatttt gccacggaaa gtactccaga 4550 tggattttct tgttcatcca gcctgagtgc tctgagcctc gatgagccat 4600 agatgtggaa ttatacagaa ttaagaataa tgcctccagt tcaggaaaat 4650 atgaaacaga gacaatggga atcagagcag cctaaagaat caaatgaaaa 4700 gaggcagaaa ccaagagaaa aaactattga ttctgaaaag gacctattag 4750 atgattcaga tgatgatgat attgaaatac tagaagaatg tattatttct 4800 caaagtcatc gccatgccaa acgtaaagca aaaaagccag cccagactgc 4850 ttcaaaatta cctccacctg tggcaaggaa accaagtcag ctgcctgtgt acaaacttct 4900 accatcacaa aacaggttgc aaccccaaaa gcatgttagt tttacaccgg 4950 gggatgatat gccacgggtg tattgtgttg aagggacacc 5000 tataaacttt tccacagcta catctctaag tgatctaaca atcgaatccc 5050 ctccaaatga gttagctgct ggagaaggag ttagaggagg ggcacagtca 5100 ggtgaatttg aaaaacgaga taccattcct acagaa GGCA gaagtacaga 5150 ggaggaaaaa tgaggctcaa cctcatctgt aaccatacct gaattggatg 5200 acaataaagc agaggaaggt gatattcttg cagaatgcat taattctgct 5250 ggaaaagtca atgcccaaag cgtgtgaaaa caagcctttc agataatgga 5300 ccaggtccag caagcatctg cgtcttcttc tgcacccaac aaaaatcagt 5350 gaaaaagaaa tagatggtaa ccaacttcac cagtaaaacc tataccacaa 5400 aatactgaat ataggacacg tgtaagaaaa aatgcagact caaaaaataa 5450 tttaaatgct gagagagttt tctcagacaa caaagattca aagaaacaga 5500 atttgaaaaa taattccaag gtcttcaatg ataagctccc aaataatgaa 5550 gatagagtca gaggaagttt tgcttttgat tcacctcatc attacacgcc 5600 tattgaagga actccttact gtttttcacg aaatgattct ttgagttctc 5650 tagattttga tgatgatgat gttgaccttt ccagggaaaa ggctgaatta 5700 aagaaaataa agaaaggcaa ggaatcagag gctaaagtta ccagccacac 5750 agaactaacc tccaaccaac aatcagctaa gctattgcaa taagacacaa 5800 agcagccaat aaatcgaggt cagcctaaac ccatacttca gaaacaatcc 5850 agtcatccaa acttttcccc agacatacca gacagagggg cagcaactga 5900 tgaaaagtta cagaattttg ctattgaaaa tactccggtt tgcttttctc 5950 at aattcctc tctgagttct ctcagtgaca ttgaccaaga aaacaacaat 6000 aaagaaaatg aacctatcaa agagactgag ccccctgact cacagggaga 6050 accaagtaaa cctcaagcat caggctatgc tcctaaatca tttcatgttg 6100 aagatacccc agtttgtttc tcaagaaaca gttctctcag ttctcttagt 6150 attgactctg aagatgacct gttgcaggaa tgtataagct ccgcaatgcc 6200 aagccttcaa aaaaaagaaa gactcaaggg tgataatgaa aaacatagtc 6250 ccagaaatat gggtggcata ttaggtgaag atctgacact tgatttgaaa 6300 gatatacaga gaccagattc agaacatggt ctatcccctg attcagaaaa 6350 ttttgattgg aaagctattc aggaaggtgc aaattccata gtaagtagtt 6400 tacatcaagc tgctgctgct gcatgtttat ctagacaagc ttcgtctgat 6450 tcctttccct tcagattcca gaaatcagga atctctctgg gatcaccatt 6500 tcatcttaca cctgatcaag aagaaaaacc ctttacaagt aataaaggcc 6550 cacgaattct aaaaccaggg gagaaaagta cattggaaac taaaaagata 6600 gtaaaggaat gaatctgaaa caaaggagga aaaaaagttt ataaaagttt 6650 aaagttcgat gattactgga ctaattcaga aatttcaggc caaatgaaac 6700 agccccttca agcaaacatg ccttcaatct ctcgaggcag gacaatgatt 6750 catattccag gagttcgaaa tagct cctca agtacaagtc ctgtttctaa 6800 ccccttaaga aaaaggccca ctccagcctc caaaagccct agtgaaggtc 6850 aaacagccac cacttctcct agaggagcca agccatctgt gaaatcagaa 6900 ttgccaggca ttaagccctg gacatcccaa ataggtgggt caagtaaagc 6950 tcaggatcta accttctaga gagattcgac cccttcaaga cctgcccagc 7000 aaccattaag tagacctata cagtctcctg gccgaaactc aatttcccct 7050 ggtagaaatg gaataagtcc tcctaacaaa ttatctcaac ttccaaggac 7100 atcatcccct agtactgctt caactaagtc ctcaggttct ggaaaaatgt 7150 catatacatc tccaggtaga cagatgagcc aacagaacct taccaaacaa 7200 acaggtttat ccaagaatgc cagtagtatt ccaagaagtg agtctgcctc 7250 aatcagatga caaaggacta ataatggtaa tggagccaat aaaaaggtag 7300 aatgtcttca aactttctag actaaatcaa gtggaagtga atctgataga 7350 tcagaaagac ctgtattagt acgccagtca actttcatca aagaagctcc 7400 ttaagaagaa aagcccaacc aattggagga atctgcttca tttgaatctc 7450 atctagacca tttctccatc gcttctccca ctaggtccca ggcacaaact 7500 ccagttttaa gtccttccct tcctgatatg tctctatcca cacattcgtc 7550 tgttcaggct ggtggatggc gaaaactccc acctaatctc agtccca cta 7600 tgatggaaga tagagtataa ccagcaaagc gccatgatat tgcacggtct 7650 cattctgaaa gtccttctag acttccaatc aataggtcag gaacctggaa 7700 acgtgagcac agcaaacatt catcatccct tcctcgagta agcacttgga 7750 gaagaactgg aagttcatct tcaattcttt ctgcttcatc agaatccagt 7800 aaagtgagga gaaaaagcaa tgaaaaacat gtgaactcta tttcaggaac 7850 caaacaaagt aaagaaaacc aagtatccgc aaaaggaaca tggagaaaaa 7900 tgaattttct taaaagaaaa cccacaaata gtacttctca gaccgtttcc 7950 tcaggtgcta caaatggtgc tgaatcaaag actctaattt atcaaatggc 8000 acctgctgtt tctaaaacag aggatgtttg ggtgagaatt gaggactgtc 8050 ccattaacaa tcctagatct ggaagatctc ccacaggtaa tactcccccg 8100 gtgtttcaga gtgattgaca aaaggcaaat ccaaacatta aagattcaaa 8150 gcaaaacaaa agataatcag atgtgggtaa tggcagtgtt cccatgcgta 8200 ccgtgggttt ggaaaatcgc ctgaactcct ttattcaggt ggatgcccct 8250 gaccaaaaag gaactgagat aaaaccagga caaaataatc ctgtccctgt 8300 aatgaaagtt atcagagact ctatagtgga acgtacccca ttcagttcta 8350 gcagctcaag caaacacagt tcacctagtg ggactgttgc tgccagagtg 8400 actcctttta att acaaccc aagccctagg aaaagcagcg cagatagcac 8450 ttcagctcgg ccatctcaga tcccaactcc agtgaataac aacacaaaga 8500 agcgagattc caaaactgac agcacagaat ccagtggaac ccaaagtcct 8550 ctgggtctta aagcgccatt ccttgtgaca tctgtttaaa agagaggaag 8600 aatgaaacta agaaaattct atgttaatta caactgctat atagacattt 8650 gaaactttaa tgtttcaaat aagactgaaa aattttgtaa ataggtttga 8700 ttcttgttag agggtttttg ttctggaagc catatttgat agtatacttt 8750 gtcttcactg gtcttatttt gggaggcact cttgatggtt aggaaaaaaa 8800 tagtaaagcc aagtatgttt gtacagtatg ttttacatgt atttaaagta 8850 gcatcccatc ccaacttcct ttaattattg cttgtcttaa aataatgaac 8900 gaaaatatga actacagata tatattgctg ttatcaatca tttctagatt 8950 taaacttaca ataaactgac tcagggaaaa attggtattt atgcaaaaaa 9000 gtccttgtga aaatgttttt gtccatctaa catcataatt aatcatgtgg 9050 cacagtaata ctgtgaaatt tggttcccga tgaacaagtt tacccagcct 9100 gctttgcttt actgcatgaa tgaaactgat ggttcaattt cagaagtaat 9150 gattaacagt tatgtggtca catgatgtgc atagagatag ctacagtgta 9200 ctattttgtg ataatttaca aacaa ctccaaacaa aaatc tgtgtaactg 9250 taaaacattg aatgaaacta ttttacctga actagatttt atctgaaagt 9300 aggtagaatt tttgctatgc tgtaatttgt tgtatattct ggtatttgag 9350 gtgagatggc tgctctttta ttaatgagac atgaattgtg tctcaacaga 9400 acatttcaga aactaaatga ataaattatt gctgtatgta aactgttact 9450 tttgtttgaa gaaattggta gggtcttgtt tcacatttgt attaataatt 9500 gtttaaaatg cctcttttaa aagcttatat aaattttttt cttcagcttc 9550 tatgcattaa gagtaaaatt cctcttactg taataaaaac aattgaagaa 9600 gactgttgcc acttaaccat tccatgcgtt ggcacttatc tattcctgaa 9650 atttctttta tgtgattagc tcatcttgat ttttaatatt tttccactta 9700 tcttactcca aacttttttt gtaaaagtaa ctggagctca attcatgtaa 9750 agcagcctag tagcaatgca cacagactaa gcattgagca taataggccc 9800 ctctttctta acataatttc atattataga attctgtact tgaaattgat 9850 tcttagacat tgcagtctct tcgaggcttt acagtgtaaa ctgtcttgcc 9900 cttgttgcaa ccttcatctt ctgggtctga catgaacact ttttatcacc 9950 ctgtatgtta gggcaagatc tcagcagtga agtataatca gcactttgcc atgctcagaa 10000 10050 aattcaaatc acatggaact ttagaggtag atttaatacg attaagatat tcagaagtat attttagaat ccctgcctgt taaggaaact 10100 ttatttgtgg taggtacagt tctggggtac atgttaagtg tccccttata 10150 cagtggaggg aagtcttcct tcctgaagga aaataaactg acacttatta 10200 actaagataa tttacttaat atatcttccc tgatttgttt taaaagatca 10250 gagggtgact gatgatacat gcatacatat ttgttgaata aatgaaaatt 10300 tatttttagt gataagattc atacactctg tatttgggga gggaaaacct 10350 ttttaagcat ggtggggcac tcagatagga gtgaatacac ctacctggtg 10400 ccttgaaaat cacatcaagt agttaattat ctacccctta cctgtgttta 10450 taacttccag gtaatgagaa tgattttttt atgccagtaa taaagctaaa ataaaagtgc 10500 10550 tatgacttga gctaagatat ttgactccaa tgcctgtact gtgtctactg caccactttg taaacacttc aatttactat ctttgaaatg attgaccttt aaatttttgc 10600 10650 caaatgttat ctgaaattgt ctatgaatac catctacttc tgttgttttc ccaggcttcc ataaacaatg gagatacatg 10700 c 10701

<210> 3 <210> 3

<211> 13147 <211> 13147

<212> ADN <212> DNA

<213> Homo sapiens <213> Homo sapiens

<400> 3 <400> 3

ccggagcccg agccgaaggg cgagccgcaa acgctaagtc gctggccatt 50 ccggagcccg agccgaaggg cgagccgcaa acgctaagtc gctggccatt 50

ggtggacatg gcgcaggcgc gtttgctccg acgggccgaa tgttttgggg 100 ggtggacatg gcgcaggcgc gtttgctccg acgggccgaa tgttttgggg 100

cagtgttttg agcgcggaga ccgcgtgata ctggatgcgc atgggcatac 150 cagtgttttg agcgcggaga ccgcgtgata ctggatgcgc atgggcatac 150

cgtgctctgc ggctgcttgg cgttgcttct tcctccagaa gtgggcgctg 200 cgtgctctgc ggctgcttgg cgttgcttct tcctccagaa gtgggcgctg 200

ggcagtcacg cagggtttga accggaagcg ggagtaggta gctgcgtggc 250 ggcagtcacg cagggtttga accggaagcg ggagtaggta gctgcgtggc 250

taacggagaa aagaagccgt ggccgcggga ggaggcgaga ggagtcggga 300 taacggagaa aagaagccgt ggccgcggga ggaggcgaga ggagtcggga 300

tctgcgctgc agccaccgcc gcggttgata ctactttgac cttccgagtg 350 tctgcgctgc agccaccgcc gcggttgata ctactttgac cttccgagtg 350

cagtgacagt gatgtgtgtt ctgaaattgt gaaccatgag tctagtactt 400 cagtgacagt gatgtgtgtt ctgaaattgt gaaccatgag tctagtactt 400

aatgatctgc ttatctgctg ccgtcaacta gaacatgata gagctacaga 450 aatgatctgc ttatctgctg ccgtcaacta gaacatgata gagctacaga 450

acgaaagaaa gaagttgaga aatttaagcg cctgattcga gatcctgaaa 500 acgaaagaaa gaagttgaga aatttaagcg cctgattcga gatcctgaaa 500

caattaaaca tctagatcgg cattcagatt ccaaacaagg aaaatatttg 550 caattaaaca tctagatcgg cattcagatt ccaaacaagg aaaatatttg 550

aattgggatg ctgtttttag atttttacag aaatatattc agaaagaaac 600 aattgggatg ctgtttttag atttttacag aaatatattc agaaagaaac 600

agaatgtctg agaatagcaa aaccaaatgt atcagcctca acacaagcct 650 agaatgtctg agaatagcaa aaccaaatgt atcagcctca acacaagcct 650

ccaggcagaa aaagatgcag gaaatcagta gtttggtcaa atacttcatc 700 ccaggcagaa aaagatgcag gaaatcagta gtttggtcaa atacttcatc 700

aaatgtgcaa acagaagagc acctaggcta aaatgtcaag aactcttaaa 750 aaatgtgcaa acagaagagc acctaggcta aaatgtcaag aactcttaaa 750

ttatatcatg gatacagtga aagattcatc taatggtgct atttacggag 800 ttatatcatg gatacagtga aagattcatc taatggtgct atttacggag 800

ctgattgtag caacatacta ctcaaagaca ttctttctgt gagaaaatac 850 ctgattgtag caacatacta ctcaaagaca ttctttctgt gagaaaatac 850

tggtgtgaaa tatctcagca acagtggtta gaattgttct ctgtgtactt 900 tggtgtgaaa tatctcagca acagtggtta gaattgttct ctgtgtactt 900

caggctctat ctgaaacctt cacaagatgt tcatagagtt ttagtggcta 950 caggctctat ctgaaacctt cacaagatgt tcatagagtt ttagtggcta 950

gaataattca tgctgttacc aaaggatgct gttctcagac tgacggatta 1000 gaataattca tgctgttacc aaaggatgct gttctcagac tgacggatta 1000

aattccaaat ttttggactt tttttccaag gctattcagt gtgcgagaca 1050 aattccaaat ttttggactt tttttccaag gctattcagt gtgcgagaca 1050

agaaaagagc tcttcaggtc taaatcatat cttagcagct cttactatct 1100 agaaaagagc tcttcaggtc taaatcatat cttagcagct cttactatct 1100

tcctcaagac tttggctgtc aactttcgaa ttcgagtgtg tgaattagga 1150 tcctcaagac tttggctgtc aactttcgaa ttcgagtgtg tgaattagga 1150

gatgaaattc ttcccacttt gctttatatt tggactcaac ataggcttaa 1200 gatgaaattc ttcccacttt gctttatatt tggactcaac ataggcttaa 1200

tgattcttta aaagaagtca ttattgaatt atttcaactg caaatttata 1250 tccatcatcc gaaaggagcc aaaacccaag aaaaaggtgc ttatgaatca 1300 acaaaatgga gaagtatttt atacaactta tatgatctgc tagtgaatga 1350 gataagtcat ataggaagta gaggaaagta ttcttcagga tttcgtaata 1400 ttgccgtcaa agaaaatttg attgaattga tggcagatat ctgtcaccag 1450 gtttttaatg aagataccag atccttggag atttctcaat cttacactac 1500 tacacaaaga gaatctagtg attacagtgt cccttgcaaa aggaagaaaa 1550 tagaactagg ctgggaagta ataaaagatc accttcagaa gtcacagaat 1600 gattttgatc ttgtgccttg gctacagatt gcaacccaat taatatcaaa 1650 gtatcctgca agtttaccta actgtgagct gtctccatta ctgatgatac 1700 tatctcagct tctaccccaa cagcgacatg gggaacgtac accatatgtg 1750 ttacgatgcc ttacggaagt tgcattgtgt caagacaaga ggtcaaacct 1800 agaaagctca caaaagtcag atttattaaa actctggaat aaaatttggt 1850 gtattacctt tcgtggtata agttctgagc aaatacaagc tgaaaacttt 1900 ggcttacttg gagccataat tcagggtagt ttagttgagg ttgacagaga 1950 attctggaag ttatttactg ggtcagcctg cagaccttca tgtcctgcag 2000 tatgctgttt gactttggca ctgaccacca gtatagttcc aggaacggta 2050 aaaatgggaa tagagcaaaa tatgtgtgaa gtaaatagaa gcttttcttt 2100 aaaggaatca ataatgaaat ggctcttatt ctatcagtta gagggtgact 2150 tagaaaatag cacagaagtg cctccaattc ttcacagtaa ttttcctcat 2200 cttgtactgg agaaaattct tgtgagtctc actatgaaaa actgtaaagc 2250 tgcaatgaat tttttccaaa gcgtgccaga atgtgaacac caccaaaaag 2300 ataaagaaga actttcattc tcagaagtag aagaactatt tcttcagaca 2350 acttttgaca agatggactt tttaaccatt gtgagagaat gtggtataga 2400 aaagcaccag tccagtattg gcttctctgt ccaccagaat ctcaaggaat 2450 cactggatcg ctgtcttctg ggattatcag aacagcttct gaataattac 2500 tcatctgaga ttacaaattc agaaactctt gtccggtgtt cacgtctttt 2550 ggtgggtgtc cttggctgct actgttacat gggtgtaata gctgaagagg 2600 aagcatataa gtcagaatta ttccagaaag ccaagtctct aatgcaatgt 2650 gcaggagaaa gtatcactct gtttaaaaat aagacaaatg aggaattcag 2700 aattggttcc ttgagaaata tgatgcagct atgtacacgt tgcttgagca 2750 actgtaccaa gaagagtcca aataagattg catctggctt tttcctgcga 2800 ttgttaacat caaagctaat gaatgacatt gcagatattt gtaaaagttt 2850 agcatccttc atcaaaaagc catttgaccg tggagaagta gaatcaatgg 2900 aagatgatac taatggaaat ctaatggagg tggaggatca gtcatccatg 2950 aatctattta acgattaccc tgatagtagt gttagtgatg caaacgaacc 3000 tggagagagc caaagtacca taggtgccat taatccttta gctgaagaat 3050 atctgtcaaa gcaagatcta cttttcttag acatgctcaa gttcttgtgt 3100 ttgtgtgtaa ctactgctca gaccaatact gtgtccttta gggcagctga 3150 tattcggagg aaattgttaa tgttaattga ttctagcacg ctagaaccta 3200 ccaaatccct ccacctgcat atgtatctaa tgcttttaaa ggagcttcct 3250 ggagaagagt accccttgcc aatggaagat gttcttgaac ttctgaaacc 3300 actatccaat gtgtgttctt tgtatcgtcg tgaccaagat gtttgtaaaa 3350 ctattttaaa ccatgtcctt catgtagtga aaaacctagg tcaaagcaat 3400 atggactctg agaacacaag ggatgctcaa ggacagtttc ttacagtaat 3450 tggagcattt tggcatctaa caaaggagag gaaatatata ttctctgtaa 3500 gaatggccct agtaaattgc cttaaaactt tgcttgaggc tgatccttat 3550 tcaaaatggg ccattcttaa tgtaatggga aaagactttc ctgtaaatga 3600 agtatttaca caatttcttg ctgacaatca tcaccaagtt cgcatgttgg 3650 ctgcagagtc aatcaataga ttgttccagg acacgaaggg agattcttcc 3700 aggttactga aagcacttcc tttgaagctt cagcaaacag cttttgaaaa 3750 tgcatacttg aaagctcagg aaggaatgag agaaatgtcc catagtgctg 3800 agaaccctga aactttggat gaaatttata atagaaaatc tgttttactg 3850 acgttgatag ctgtggtttt atcctgtagc cctatctgcg aaaaacaggc 3900 tttgtttgcc ctgtgtaaat ctgtgaaaga gaatggatta gaacctcacc 3950 ttgtgaaaaa ggttttagag aaagtttctg aaacttttgg atatagacgt 4000 ttagaagact ttatggcatc tcatttagat tatctggttt tggaatggct 4050 aaatcttcaa gatactgaat acaacttatc ttcttttcct tttattttat 4100 taaactacac aaatattgag gatttctata gatcttgtta taaggttttg 4150 attccacatc tggtgattag aagtcatttt gatgaggtga agtccattgc 4200 taatcagatt caagaggact ggaaaagtct tctaacagac tgctttccaa 4250 agattcttgt aaatattctt ccttattttg cctatgaggg taccagagac 4300 agtgggatgg cacagcaaag agagactgct accaaggtct atgatatgct 4350 taaaagtgaa aacttattgg gaaaacagat tgatcactta ttcattagta 4400 atttaccaga gattgtggtg gagttattga tgacgttaca tgagccagca 4450 aattctagtg ccagtcagag cactgacctc tgtgactttt caggggattt 4500 ggatcctgct cctaatccac ctcattttcc atcgcatgtg attaaagcaa 4550 catttgccta tatcagcaat tgtcataaaa ccaagttaaa aagcatttta 4600 gaaattcttt ccaaaagccc tgattcctat cagaaaattc ttcttgccat 4650 atgtgagcaa gcagctgaaa caaataatgt ttataagaag cacagaattc 4700 ttaaaatata tcacctgttt gttagtttat tactgaaaga tataaaaagt 4750 ggcttaggag gagcttgggc ctttgttctt cgagacgtta tttatacttt 4800 gattcactat atcaaccaaa ggccttcttg tatcatggat gtgtcattac 4850 gtagcttctc cctttgttgt gacttattaa gtcaggtttg ccagacagcc 4900 gtgacttact gtaaggatgc tctagaaaac catcttcatg ttattgttgg 4950 tacacttata ccccttgtgt atgagcaggt ggaggttcag aaacaggtat 5000 tggacttgtt gaaatactta gtgatagata acaaggataa tgaaaacctc 5050 tatatcacga ttaagctttt agatcctttt cctgaccatg ttgtttttaa 5100 ggatttgcgt attactcagc aaaaaatcaa atacagtaga ggaccctttt 5150 cactcttgga ggaaattaac cattttctct cagtaagtgt ttatgatgca 5200 cttccattga caagacttga aggactaaag gatcttcgaa gacaactgga 5250 actacataaa gatcagatgg tggacattat gagagcttct caggataatc 5300 cgcaagatgg gattatggtg aaactagttg tcaatttgtt gcagttatcc 5350 aagatggcaa taaaccacac tggtgaaaaa gaagttctag aggctgttgg 5400 aagctgcttg ggagaagtgg gtcctataga tttctctacc atagctatac 5450 aacatagtaa agatgcatct tataccaagg cccttaagtt atttgaagat 5500 aaagaacttc agtggacctt cataatgctg acctacctga ataacacact 5550 ggtagaagat tgtgtcaaag ttcgatcagc agctgttacc tgtttgaaaa 5600 acattttagc cacaaagact ggacatagtt tctgggagat ttataagatg 5650 acaacagatc caatgctggc ctatctacag ccttttagaa catcaagaaa 5700 aaagttttta gaagtaccca gatttgacaa agaaaaccct tttgaaggcc 5750 tggatgatat aaatctgtgg attcctctaa gtgaaaatca tgacatttgg 5800 ataaagacac tgacttgtgc ttttttggac agtggaggca caaaatgtga 5850 aattcttcaa ttattaaagc caatgtgtga agtgaaaact gacttttgtc 5900 agactgtact tccatacttg attcatgata ttttactcca agatacaaat 5950 gaatcatgga gaaatctgct ttctacacat gttcagggat ttttcaccag 6000 ctgtcttcga cacttctcgc aaacgagccg atccacaacc cctgcaaact 6050 tggattcaga gtcagagcac tttttccgat gctgtttgga taaaaaatca 6100 caaagaacaa tgcttgctgt tgtggactac atgagaagac aaaagagacc 6150 ttcttcagga acaattttta atgatgcttt ctggctggat ttaaattatc 6200 tagaagttgc caaggtagct cagtcttgtg ctgctcactt tacagcttta 6250 ctctatgcag aaatctatgc agataagaaa agtatggatg atcaagagaa 6300 aagaagtctt gcatttgaag aaggaagcca gaatacaact atttctagct 6350 tgagtgaaaa aagtaaagaa gaaactggaa taagtttaca ggatcttctc 6400 ttagaaatct acagaagtat aggggagcca gatagtttgt atggctgtgg 6450 tggagggaag atgttacaac ccattactag actacgaaca tatgaacacg 6500 aagcaatgtg gggcaaagcc ctagtaacat atgacctcga aacagcaatc 6550 ccctcatcaa cacgccaggc aggaatcatt caggccttgc agaatttggg 6600 actctgccat attctttccg tctatttaaa aggattggat tatgaaaata 6650 aagactggtg tcctgaacta gaagaacttc attaccaagc agcatggagg 6700 aatatgcagt gggaccattg cacttccgtc agcaaagaag tagaaggaac 6750 cagttaccat gaatcattgt acaatgctct acaatctcta agagacagag 6800 aattctctac attttatgaa agtctcaaat atgccagagt aaaagaagtg 6850 gaagagatgt gtaagcgcag ccttgagtct gtgtattcgc tctatcccac 6900 acttagcagg ttgcaggcca ttggagagct ggaaagcatt ggggagcttt 6950 tctcaagatc agtcacacat agacaactct ctgaagtata tattaagtgg 7000 cagaaacact cccagcttct caaggacagt gattttagtt ttcaggagcc 7050 tatcatggct ctacgcacag tcattttgga gatcctgatg gaaaaggaaa 7100 tggacaactc acaaagagaa tgtattaagg acattctcac caaacacctt 7150 gtagaactct ctatactggc cagaactttc aagaacactc agctccctga 7200 aagggcaata tttcaaatta aacagtacaa ttcagttagc tgtggagtct 7250 ctgagtggca gctggaagaa gcacaagtat tctgggcaaa aaaggagcag 7300 agtcttgccc tgagtattct caagcaaatg atcaagaagt tggatgccag 7350 ctgtgcagcg aacaatccca gcctaaaact tacatacaca gaatgtctga 7400 gggtttgtgg caactggtta gcagaaacgt gcttagaaaa tcctgcggtc 7450 atcatgcaga cctatctaga aaaggcagta gaagttgctg gaaattatga 7500 tggagaaagt agtgatgagc taagaaatgg aaaaatgaag gcatttctct 7550 cattagcccg gttttcagat actcaatacc aaagaattga aaactacatg 7600 aaatcatcgg aatttgaaaa caagcaagct ctcctgaaaa gagccaaaga 7650 ggaagtaggt ctccttaggg aacataaaat tcagacaaac agatacacag 7700 taaaggttca gcgagagctg gagttggatg aattagccct gcgtgcactg 7750 aaagaggatc gtaaacgctt cttatgtaaa gcagttgaaa attatatcaa 7800 ctgcttatta agtggagaag aacatgatat gtgggtattc cgactttgtt 7850 ccctctggct tgaaaattct ggagtttctg aagtcaatgg catgatgaag 7900 gcaaacggaa tgaagattcc aacatataaa tttttgcctc ttatgtacca 7950 attggctgct agaatgggga ccaagatgat gggaggccta ggatttcatg 8000 aagtcctcaa taatctaatc tctagaattt caatggatca cccccatcac 8050 actttgttta ttatactggc cttagcaaat gcaaacagag atgaatttct 8100 gactaaacca gaggtagcca gaagaagcag aataactaaa aatgtgccta 8150 aacaaagctc tcagcttgat gaggatcgaa cagaggctgc aaatagaata 8200 atatgtacta tcagaagtag gagacctcag atggtcagaa gtgttgaggc 8250 actttgtgat gcttatatta tattagcaaa cttagatgcc actcagtgga 8300 agactcagag aaaaggcata aatattccag cagaccagcc aattactaaa 8350 cttaagaatt tagaagatgt tgttgtccct actatggaaa ttaaggtgga 8400 ccacacagga gaatatggaa atctggtgac tatacagtca tttaaagcag 8450 aatttcgctt agcaggaggt gtaaatttac caaaaataat agattgtgta 8500 ggttccgatg gcaaggagag gagacagctt gttaagggcc gtgatgacct 8550 gagacaagat gctgtcatgc aacaggtctt ccagatgtgt aatacattac 8600 tgcagagaaa cacggaaact aggaagagga aattaactat ctgtacttat 8650 aaggtggttc ccctctctca gcgaagtggt gttcttgaat ggtgcacagg 8700 aactgtcccc attggtgaat ttcttgttaa caatgaagat ggtgctcata 8750 aaagatacag gccaaatgat ttcagtgcct ttcagtgcca aaagaaaatg 8800 atggaggtgc aaaaaaagtc ttttgaagag aaatatgaag tcttcatgga 8850 tgtttgccaa aattttcaac cagttttccg ttacttctgc atggaaaaat 8900 tcttggatcc agctatttgg tttgagaagc gattggctta tacgcgcagt 8950 gtagctactt cttctattgt tggttacata cttggacttg gtgatagaca 9000 tgtacagaat atcttgataa atgagcagtc agcagaactt gtacatatag 9050 atctaggtgt tgcttttgaa cagggcaaaa tccttcctac tcctgagaca 9100 gttcctttta gactcaccag agatattgtg gatggcatgg gcattacggg 9150 tgttgaaggt gtcttcagaa gatgctgtga gaaaaccatg gaagtgatga 9200 gaaactctca ggaaactctg ttaaccattg tagaggtcct tctatatgat 9250 ccactctttg actggaccat gaatcctttg aaagctttgt atttacagca 9300 gaggccggaa gatgaaactg agcttcaccc tactctgaat gcagatgacc 9350 aagaatgcaa acgaaatctc agtgatattg accagagttt caacaaagta 9400 gctgaacgtg tcttaatgag actacaagag aaactgaaag gagtggaaga 9450 aggcactgtg ctcagtgttg gtggacaagt gaatttgctc atacagcagg 9500 ccatagaccc caaaaatctc agccgacttt tcccaggatg gaaagcttgg 9550 gtgtgatctt cagtatatga attacccttt cattcagcct ttagaaatta 9600 tattttagcc tttattttta acctgccaac atactttaag tagggattaa 9650 tatttaagtg aactattgtg ggtttttttg aatgttggtt ttaatacttg 9700 atttaatcac cactcaaaaa tgttttgatg gtcttaagga acatctctgc 9750 tttcactctt tagaaataat ggtcattcgg gctgggcgca gcggctcacg 9800 cctgtaatcc cagcactttg ggaggccgag gtgagcggat cacaaggtca 9850 ggagttcgag accagcctgg ccaagagacc agcctggcca gtatggtgaa 9900 accctgtctc tactaaaaat acaaaaatta gccgagcatg gtggcgggca 9950 cctgtaatcc cagctactcg agaggctgag gcaggagaat ctcttgaacc 10000 tgggaggtga aggttgctgt gggccaaaat catgccattg cactccagcc 10050 tgggtgacaa gagcgaaact ccatctcaaa aaaaaaaaaa aaaaaacaga 10100 aacgtatttg gatttttcct agtaagatca ctcagtgtta ctaaataatg 10150 aagttgttat ggagaacaaa tttcaaagac acagttagtg tagttactat 10200 ttttttaagt gtgtattaaa acttctcatt ctattctctt tatcttttaa 10250 gcccttctgt actgtccatg tatgttatct ttctgtgata acttcataga 10300 ttgccttcta gttcatgaat tctcttgtca gatgtatata atctctttta 10350 ccctatccat tgggcttctt ctttcagaaa ttgtttttca tttctaatta 10400 tgcatcattt ttcagatctc tgtttcttga tgtcattttt aatgtttttt 10450 taatgttttt tatgtcacta attattttaa atgtctgtac ttgatagaca 10500 ctgtaatagt tctattaaat ttagttcctg ctgtttatat ctgttgattt 10550 ttgtatttga taggctgttc atccagtttt gtctttttga aaagtgagtt 10600 tattttcagc aaggctttat ctatgggaat cttgagtgtc tgtttatgtc 10650 atattcccag ggctgttgct gcacacaagc ccattcttat tttaatttct 10700 tggctttagg gtttccatac ctgaagtgta gcataaatac tgataggaga 10750 tttcccaggc caaggcaaac acacttcctc ctcatctcct tgtgctagtg 10800 ggcagaatat ttgattgatg cctttttcac tgagagtata agcttccatg 10850 tgtcccacct ttatggcagg ggtggaagga ggtacattta attcccactg 10900 cctgcctttg gcaagccctg ggttctttgc tccccatata gatgtctaag 10950 ctaaaagccg tgggttaatg agactggcaa attgttccag gacagctaca 11000 gcatcagctc acatattcac ctctctggtt tttcattccc ctcatttttt 11050 tctgagacag agtcttgctc tgtcacccag gctggagtgc agtggcatga 11100 tctcagctca ctgaaacctc tgcctcctgg gttcaagcaa ttctcctgcc 11150 tcagcctccc gagtagctgg gactacaggc gtgtgccaac acgcccggct 11200 aattttttgt atttttatta gagacggagt ttcaccgtgt tagccaggat 11250 ggtctcgatc gcttgacctc gtgatccacc ctcctcggcc tcccaaagtg 11300 ctgggattac aggtgtgagc caccgcgccc ggcctcattc ccctcatttt 11350 tgaccgtaag gatttcccct ttcttgtaag ttctgctatg tatttaaaag 11400 aatgttttct acattttatc cagcatttct ctgtgttctg ttggaaggga 11450 agggcttagg tatctagttt gatacatagg tagaagtgga acatttctct 11500 gtcccccagc tgtcatcata taagataaac atcagataaa aagccacctg 11550 aaagtaaaac tactgactcg tgtattagtg agtataatct cttctccatc 11600 cttaggaaaa tgttcatccc agctgcggag attaacaaat gggtgattga 11650 gctttctcct cgtatttgga ccttgaaggt tatataaatt tttttcttat 11700 gaagagttgg catttctttt tattgccaat ggcaggcact cattcatatt 11750 tgatctcctc accttcccct cccctaaaac caatctccag aactttttgg 11800 actataaatt tcttggtttg acttctggag aactgttcag aatattactt 11850 tgcatttcaa attacaaact taccttggtg tatctttttc ttacaagctg 11900 cctaaatgaa tatttggtat atattggtag ttttattact atagtaaatc 11950 aaggaaatgc agtaaactta aaatgtcttt aagaaagccc tgaaatcttc 12000 atgggtgaaa ttagaaatta tcaactagat aatagtatag ataaatgaat 12050 ttgtagctaa ttcttgctag ttgttgcatc cagagagctt tgaataacat 12100 cattaatcta ctctttagcc ttgcatggta tgctatgagg ctcctgttct 12150 gttcaagtat tctaatcaat ggctttgaaa agtttatcaa atttacatac 12200 agatcacaag cctaggagaa ataactaatt cacagatgac agaattaaga 12250 ttataaaaga tttttttttt gtaattttag tagagacagg gttgccattg 12300 tattccagcc ttggcgacag agcaagactc tgcctcaaaa aaaaaaaaaa 12350 aaaggttttg gcaagctgga actctttctg caaatgacta agatagaaaa 12400 ctgccaagga caaatgagga gtagttagat tttgaaaata ttaatcatag 12450 aatagttgtt gtatgctaag tcactgaccc atattatgta cagcatttct 12500 gatctttact ttgcaagatt agtgatacta tcccaataca ctgctggaga 12550 aatcagaatt tggagaaata agttgtccaa ggcaagaaga tagtaaatta 12600 taagtacaag tgtaatatgg acagtatcta acttgaaaag atttcaggcg 12650 aaaagaatct ggggtttgcc agtcagttgc tcaaaaggtc aatgaaaacc 12700 aaatagtgaa gctatcagag aagctaataa attatagact gcttgaacag 12750 ttgtgtccag attaagggag ataatagctt tcccacccta ctttgtgcag 12800 gtcatacctc cccaaagtgt ttacctaatc agtaggttca caaactcttg 12850 gtcattatag tatatgccta aaatgtatgc acttaggaat gctaaaaatt 12900 taaatatggt ctaaagcaaa taaaagcaaa gaggaaaaac tttggacagc 12950 gtaaagacta gaatagtctt ttaaaaagaa agccagtata ttggtttgaa 13000 atatagagat gtgtcccaat ttcaagtatt ttaattgcac cttaatgaaa 13050 ttatctattt tctatagatt ttagtactat tgaatgtatt actttactgt 13100 tacctgaatt tattataaag tgtttttgaa taaataattc taaaagc 13147 tgattcttta aaagaagtca ttattgaatt atttcaactg caaatttata 1250 tccatcatcc gaaaggagcc aaaacccaag aaaaaggtgc ttatgaatca 1300 acaaaatgga gaagtatttt atacaactta tatgatctgc tagtgaatga 1350 ataggaagta gataagtcat gaggaaagta ttcttcagga tttcgtaata 1400 ttgccgtcaa agaaaatttg attgaattga tggcagatat ctgtcaccag 1450 gtttttaatg aagataccag atccttggag atttctcaat cttacactac 1500 tacacaaaga gaatctagtg attacagtgt cccttgcaaa aggaagaaaa 1550 tagaactagg ctgggaagta ataaaagatc accttcagaa gtcacagaat 1600 gattttgatc ttgtgccttg gctacagatt gcaacccaat taatatcaaa 1650 agtttaccta gtatcctgca actgtgagct gtctccatta ctgatgatac 1700 tatctcagct tctaccccaa cagcgacatg gggaacgtac accatatgtg 1750 ttacgatgcc ttacggaagt tgcattgtgt caagacaaga ggtcaaacct 1800 agaaagctca caaaagtcag atttattaaa actctggaat aaaatttggt 1850 gtattacctt tcgtggtata agttctgagc aaatacaagc tgaaaacttt 1900 ggcttacttg gagccataat tcagggtagt ttagttgagg ttgacagaga 1950 attctggaag ttatttactg ggtcagcctg cagaccttca tgtcctgcag 2000 tatgctgttt gactttggca ct gaccacca gtatagttcc aggaacggta 2050 tagagcaaaa aaaatgggaa tatgtgtgaa gtaaatagaa gcttttcttt 2100 aaaggaatca ataatgaaat ggctcttatt ctatcagtta gagggtgact 2150 tagaaaatag cacagaagtg cctccaattc ttcacagtaa ttttcctcat 2200 cttgtactgg agaaaattct tgtgagtctc actatgaaaa actgtaaagc 2250 tgcaatgaat tttttccaaa gcgtgccaga atgtgaacac caccaaaaag 2300 ataaagaaga actttcattc tcagaagtag aagaactatt tcttcagaca 2350 acttttgaca agatggactt tttaaccatt gtgagagaat gtggtataga 2400 aaagcaccag tccagtattg gcttctctgt ccaccagaat ctcaaggaat 2450 cactggatcg ctgtcttctg ggattatcag aacagcttct gaataattac 2500 tcatctgaga ttacaaattc agaaactctt gtccggtgtt cacgtctttt 2550 ggtgggtgtc cttggctgct actgttacat gggtgtaata gctgaagagg 2600 gtcagaatta aagcatataa ttccagaaag ccaagtctct aatgcaatgt 2650 gcaggagaaa gtatcactct gtttaaaaat aagacaaatg aggaattcag 2700 aattggttcc ttgagaaata tgatgcagct atgtacacgt tgcttgagca 2750 gaagagtcca actgtaccaa aataagattg catctggctt tttcctgcga 2800 ttgttaacat caaagctaat gaatgacatt gcagatattt gtaaa agttt 2850 agcatccttc atcaaaaagc catttgaccg tggagaagta gaatcaatgg 2900 aagatgatac taatggaaat ctaatggagg tggaggatca gtcatccatg 2950 aatctattta acgattaccc tgatagtagt gttagtgatg caaacgaacc 3000 tggagagagc caaagtacca taggtgccat taatccttta gctgaagaat 3050 gcaagatcta atctgtcaaa cttttcttag acatgctcaa gttcttgtgt 3100 ctactgctca ttgtgtgtaa gaccaatact gtgtccttta gggcagctga 3150 tattcggagg aaattgttaa tgttaattga ttctagcacg ctagaaccta 3200 ccaaatccct ccacctgcat atgtatctaa tgcttttaaa ggagcttcct 3250 ggagaagagt accccttgcc aatggaagat gttcttgaac ttctgaaacc 3300 actatccaat gtgtgttctt tgtatcgtcg tgaccaagat gtttgtaaaa 3350 ctattttaaa ccatgtcctt catgtagtga aaaacctagg tcaaagcaat 3400 atggactctg agaacacaag ggatgctcaa ggacagtttc ttacagtaat 3450 tggcatctaa tggagcattt caaaggagag gaaatatata ttctctgtaa 3500 gaatggccct agtaaattgc cttaaaactt tgcttgaggc tgatccttat 3550 ccattcttaa tcaaaatggg tgtaatggga aaagactttc ctgtaaatga 3600 agtatttaca caatttcttg ctgacaatca tcaccaagtt cgcatgttgg 3650 ctgcagagtc aa tcaataga ttgttccagg acacgaaggg agattcttcc 3700 aggttactga aagcacttcc tttgaagctt cagcaaacag cttttgaaaa 3750 tgcatacttg aaagctcagg aaggaatgag agaaatgtcc catagtgctg 3800 agaaccctga aactttggat gaaatttata atagaaaatc tgttttactg 3850 acgttgatag ctgtggtttt atcctgtagc cctatctgcg aaaaacaggc 3900 tttgtttgcc ctgtgtaaat ctgtgaaaga gaatggatta gaacctcacc 3950 ttgtgaaaaa ggttttagag aaagtttctg aaacttttgg atatagacgt 4000 ttagaagact ttatggcatc tcatttagat tatctggttt tggaatggct 4050 aaatcttcaa gatactgaat acaacttatc ttcttttcct tttattttat 4100 taaactacac aaatattgag gatttctata gatcttgtta taaggttttg 4150 attccacatc tggtgattag aagtcatttt gatgaggtga agtccattgc 4200 taatcagatt caagaggact ggaaaagtct tctaacagac tgctttccaa 4250 agattcttgt aaatattctt ccttattttg cctatgaggg taccagagac 4300 agtgggatgg cacagcaaag agagactgct accaaggtct atgatatgct 4350 taaaagtgaa aacttattgg gaaaacagat tgatcactta ttcattagta 4400 gattgtggtg atttaccaga tgacgttaca gagttattga tgagccagca 4450 aattctagtg ccagtcagag cactgacctc tgtg actttt caggggattt 4500 ggatcctgct cctaatccac ctcattttcc atcgcatgtg attaaagcaa 4550 catttgccta tatcagcaat tgtcataaaa ccaagttaaa aagcatttta 4600 gaaattcttt ccaaaagccc tgattcctat cagaaaattc ttcttgccat 4650 gcagctgaaa atgtgagcaa caaataatgt ttataagaag cacagaattc 4700 ttaaaatata tcacctgttt gttagtttat tactgaaaga tataaaaagt 4750 ggcttaggag gagcttgggc ctttgttctt cgagacgtta tttatacttt 4800 gattcactat atcaaccaaa ggccttcttg tatcatggat gtgtcattac 4850 gtagcttctc cctttgttgt gacttattaa gtcaggtttg ccagacagcc 4900 gtgacttact gtaaggatgc tctagaaaac catcttcatg ttattgttgg tacacttata 4950 ccccttgtgt atgagcaggt ggaggttcag aaacaggtat 5000 gaaatactta tggacttgtt acaaggataa gtgatagata tgaaaacctc 5050 tatatcacga ttaagctttt agatcctttt cctgaccatg ttgtttttaa 5100 ggatttgcgt attactcagc aaaaaatcaa atacagtaga ggaccctttt 5150 cactcttgga ggaaattaac cattttctct cagtaagtgt ttatgatgca 5200 caagacttga cttccattga aggactaaag gatcttcgaa gacaactgga 5250 actacataaa gatcagatgg tggacattat gagagcttct caggataatc 5300 cgcaagatgg gattatggtg aaactagttg tcaatttgtt gcagttatcc 5350 aagatggcaa taaaccacac tggtgaaaaa gaagttctag aggctgttgg 5400 aagctgcttg ggagaagtgg gtcctataga tttctctacc atagctatac 5450 aacatagtaa agatgcatct tataccaagg cccttaagtt atttgaagat 5500 aaagaacttc agtggacctt cataatgctg acctacctga ataacacact 5550 ggtagaagat tgtgtcaaag ttcgatcagc agctgttacc tgtttgaaaa 5600 acattttagc cacaaagact ggacatagtt tctgggagat ttataagatg 5650 acaacagatc caatgctggc ctatctacag ccttttagaa catcaagaaa 5700 gaagtaccca aaagttttta gatttgacaa agaaaaccct tttgaaggcc 5750 tggatgatat aaatctgtgg attcctctaa gtgaaaatca tgacatttgg 5800 ataaagacac tgacttgtgc ttttttggac agtggaggca caaaatgtga 5850 ttattaaagc aattcttcaa caatgtgtga agtgaaaact gacttttgtc 5900 agactgtact tccatacttg attcatgata ttttactcca agatacaaat 5950 gaatcatgga gaaatctgct ttctacacat gttcagggat ttttcaccag 6000 ctgtcttcga cacttctcgc aaacgagccg atccacaacc cctgcaaact 6050 tggattcaga gtcagagcac tttttccgat taaaaaatca gctgtttgga 6100 caaagaacaa tgcttgctgt tg tggactac atgagaagac aaaagagacc 6150 acaattttta ttcttcagga atgatgcttt ctggctggat ttaaattatc 6200 tagaagttgc caaggtagct cagtcttgtg ctgctcactt tacagcttta 6250 ctctatgcag aaatctatgc agataagaaa agtatggatg atcaagagaa 6300 aagaagtctt gcatttgaag aaggaagcca gaatacaact atttctagct 6350 tgagtgaaaa aagtaaagaa taagtttaca gaaactggaa ggatcttctc 6400 ttagaaatct acagaagtat aggggagcca gatagtttgt atggctgtgg 6450 tggagggaag atgttacaac ccattactag actacgaaca tatgaacacg 6500 aagcaatgtg gggcaaagcc ctagtaacat atgacctcga aacagcaatc 6550 ccctcatcaa cacgccaggc aggaatcatt caggccttgc agaatttggg 6600 actctgccat attctttccg tctatttaaa aggattggat tatgaaaata 6650 aagactggtg tcctgaacta gaagaacttc attaccaagc agcatggagg 6700 aatatgcagt gggaccattg cacttccgtc agcaaagaag tagaaggaac 6750 cagttaccat gaatcattgt acaatgctct acaatctcta agagacagag 6800 aattctctac attttatgaa agtctcaaat atgccagagt aaaagaagtg 6850 gaagagatgt gtaagcgcag ccttgagtct gtgtattcgc tctatcccac 6900 acttagcagg ttgcaggcca ttggagagct ggaaagcatt gggg agcttt 6950 tctcaagatc agtcacacat agacaactct ctgaagtata tattaagtgg 7000 cagaaacact cccagcttct caaggacagt gattttagtt ttcaggagcc 7050 tatcatggct ctacgcacag tcattttgga gatcctgatg gaaaaggaaa 7100 tggacaactc acaaagagaa tgtattaagg acattctcac caaacacctt 7150 gtagaactct ctatactggc cagaactttc aagaacactc agctccctga 7200 tttcaaatta aagggcaata aacagtacaa ttcagttagc tgtggagtct 7250 gctggaagaa ctgagtggca gcacaagtat tctgggcaaa aaaggagcag 7300 agtcttgccc tgagtattct caagcaaatg atcaagaagt tggatgccag 7350 ctgtgcagcg aacaatccca tacatacaca gcctaaaact gaatgtctga 7400 gggtttgtgg caactggtta gcagaaacgt gcttagaaaa tcctgcggtc 7450 cctatctaga atcatgcaga aaaggcagta gaagttgctg gaaattatga 7500 tggagaaagt agtgatgagc taagaaatgg aaaaatgaag gcatttctct 7550 cattagcccg gttttcagat actcaatacc aaagaattga aaactacatg 7600 aaatcatcgg aatttgaaaa ctcctgaaaa caagcaagct gagccaaaga 7650 ggaagtaggt ctccttaggg aacataaaat tcagacaaac agatacacag 7700 taaaggttca gcgagagctg gagttggatg aattagccct gcgtgcactg 7750 aaagaggatc g taaacgctt gcagttgaaa cttatgtaaa attatatcaa 7800 ctgcttatta agtggagaag aacatgatat gtgggtattc cgactttgtt 7850 ccctctggct tgaaaattct ggagtttctg aagtcaatgg catgatgaag 7900 gcaaacggaa tgaagattcc aacatataaa tttttgcctc ttatgtacca 7950 attggctgct agaatgggga ccaagatgat gggaggccta ggatttcatg 8000 aagtcctcaa taatctaatc tctagaattt caatggatca cccccatcac 8050 actttgttta ttatactggc cttagcaaat gcaaacagag atgaatttct 8100 gactaaacca gaggtagcca aataactaaa gaagaagcag aatgtgccta 8150 aacaaagctc tcagcttgat gaggatcgaa cagaggctgc aaatagaata 8200 atatgtacta tcagaagtag gagacctcag atggtcagaa gtgttgaggc 8250 actttgtgat gcttatatta tattagcaaa cttagatgcc actcagtgga 8300 agactcagag aaaaggcata aatattccag cagaccagcc aattactaaa 8350 cttaagaatt tagaagatgt tgttgtccct ttaaggtgga actatggaaa 8400 gaatatggaa ccacacagga atctggtgac tatacagtca tttaaagcag 8450 aatttcgctt agcaggaggt gtaaatttac caaaaataat agattgtgta 8500 ggttccgatg gcaaggagag gagacagctt gttaagggcc gtgatgacct cca 8550 gagacaagat gctgtcatgc aacaggtctt gatgtgt aatacattac 8600 tgcagagaaa cacggaaact aggaagagga aattaactat ctgtacttat 8650 ccctctctca aaggtggttc gcgaagtggt gttcttgaat ggtgcacagg 8700 aactgtcccc attggtgaat ttcttgttaa caatgaagat ggtgctcata 8750 aaagatacag gccaaatgat ttcagtgcct ttcagtgcca aaagaaaatg 8800 atggaggtgc aaaaaaagtc ttttgaagag aaatatgaag tcttcatgga 8850 tgtttgccaa aattttcaac cagttttccg ttacttctgc atggaaaaat 8900 tcttggatcc agctatttgg tttgagaagc gattggctta tacgcgcagt 8950 gtagctactt cttctattgt tggttacata cttggacttg gtgatagaca 9000 tgtacagaat atcttgataa atgagcagtc agcagaactt gtacatatag 9050 tgcttttgaa atctaggtgt cagggcaaaa tccttcctac tcctgagaca 9100 gttcctttta gactcaccag agatattgtg gatggcatgg gcattacggg 9150 gtcttcagaa tgttgaaggt gatgctgtga gaaaaccatg gaagtgatga 9200 gaaactctca ggaaactctg ttaaccattg tagaggtcct tctatatgat 9250 ccactctttg actggaccat gaatcctttg aaagctttgt atttacagca 9300 gaggccggaa gatgaaactg agcttcaccc tactctgaat gcagatgacc 9350 aagaatgcaa acgaaatctc agtgatattg accagagttt caacaaagta 9400 gctgaacgtg tcttaatgag actacaagag aaactgaaag gagtggaaga 9450 aggcactgtg ctcagtgttg gtggacaagt gaatttgctc atacagcagg 9500 ccatagaccc caaaaatctc agccgacttt tcccaggatg gaaagcttgg 9550 gtgtgatctt cagtatatga attacccttt cattcagcct ttagaaatta 9600 tattttagcc tttattttta acctgccaac atactttaag tagggattaa 9650 tatttaagtg aactattgtg ggtttttttg aatgttggtt ttaatacttg 9700 atttaatcac cactcaaaaa tgttttgatg gtcttaagga acatctctgc 9750 tttcactctt tagaaataat ggtcattcgg gctgggcgca gcggctcacg 9800 cctgtaatcc cagcactttg ggaggccgag gtgagcggat cacaaggtca 9850 ggagttcgag accagcctgg ccaagagacc agcctggcca gtatggtgaa 9900 accctgtctc tactaaaaat acaaaaatta gccgagcatg gtggcgggca 9950 cctgtaatcc cagctactcg agaggctgag gcaggagaat ctcttgaacc tgggaggtga 10000 10050 aggttgctgt gggccaaaat catgccattg cactccagcc gagcgaaact tgggtgacaa aaaaaaaaaa 10100 ccatctcaaa aaaaaacaga aacgtatttg gatttttcct agtaagatca ctcagtgtta ctaaataatg aagttgttat ggagaacaaa 10150 10200 tttcaaagac acagttagtg tagttactat ttttttaagt gtgtattaa to acttctcatt ctattctctt tatcttttaa 10250 gcccttctgt actgtccatg tatgttatct ttctgtgata acttcataga 10300 gttcatgaat ttgccttcta tctcttgtca atctctttta gatgtatata 10350 ccctatccat tgggcttctt ctttcagaaa ttgtttttca tttctaatta 10400 tgcatcattt ttcagatctc tgtttcttga tgtcattttt aatgtttttt 10450 tatgtcacta taatgttttt attattttaa atgtctgtac ttgatagaca 10500 ctgtaatagt tctattaaat ttagttcctg ctgtttatat ctgttgattt 10550 ttgtatttga taggctgttc atccagtttt gtctttttga aaagtgagtt 10600 tattttcagc aaggctttat ctatgggaat cttgagtgtc tgtttatgtc atattcccag 10650 10700 ggctgttgct gcacacaagc ccattcttat tttaatttct tggctttagg gtttccatac ctgaagtgta gcataaatac tgataggaga tttcccaggc caaggcaaac 10750 10800 acacttcctc ctcatctcct tgtgctagtg ggcagaatat ttgattgatg cctttttcac tgagagtata agcttccatg tgtcccacct ttatggcagg 10850 10900 ggtggaagga ggtacattta attcccactg cctgcctttg gcaagccctg ggttctttgc tccccatata gatgtctaag ctaaaagccg tgggttaatg 10950 11000 agactggcaa attgttccag gacagctaca gcatcagctc acatattcac ctctct GGTT tttcattccc ctcatttttt 11050 tctgagacag agtcttgctc tgtcacccag gctggagtgc agtggcatga 11100 tctcagctca ctgaaacctc tgcctcctgg gttcaagcaa ttctcctgcc 11150 tcagcctccc gagtagctgg gactacaggc gtgtgccaac acgcccggct 11200 aattttttgt atttttatta gagacggagt ttcaccgtgt tagccaggat 11250 ggtctcgatc gcttgacctc gtgatccacc ctcctcggcc tcccaaagtg 11300 ctgggattac aggtgtgagc caccgcgccc ggcctcattc ccctcatttt 11350 tgaccgtaag gatttcccct ttcttgtaag ttctgctatg tatttaaaag 11400 aatgttttct acattttatc cagcatttct ctgtgttctg ttggaaggga agggcttagg 11450 11500 tatctagttt gatacatagg tagaagtgga acatttctct gtcccccagc tgtcatcata taagataaac atcagataaa aagccacctg aaagtaaaac tactgactcg 11550 11600 tgtattagtg agtataatct cttctccatc cttaggaaaa tgttcatccc agctgcggag attaacaaat gggtgattga gctttctcct cgtatttgga 11650 11700 ccttgaaggt tatataaatt tttttcttat gaagagttgg catttctttt tattgccaat ggcaggcact cattcatatt tgatctcctc 11750 11800 accttcccct cccctaaaac caatctccag aactttttgg actataaatt tcttggtttg acttctggag aac tgttcag aatattactt 11850 tgcatttcaa attacaaact taccttggtg tatctttttc ttacaagctg 11900 cctaaatgaa tatttggtat atattggtag ttttattact atagtaaatc 11950 aaggaaatgc agtaaactta aaatgtcttt aagaaagccc tgaaatcttc 12000 ttagaaatta atgggtgaaa tcaactagat aatagtatag ataaatgaat 12050 ttgtagctaa ttcttgctag ttgttgcatc cagagagctt tgaataacat 12100 cattaatcta ctctttagcc ttgcatggta tgctatgagg ctcctgttct 12150 gttcaagtat tctaatcaat ggctttgaaa agtttatcaa atttacatac 12200 agatcacaag cctaggagaa ataactaatt cacagatgac agaattaaga ttataaaaga 12250 12300 tttttttttt gtaattttag tagagacagg gttgccattg tattccagcc ttggcgacag agcaagactc tgcctcaaaa aaaggttttg aaaaaaaaaa 12350 12400 gcaagctgga actctttctg caaatgacta agatagaaaa caaatgagga ctgccaagga gtagttagat tttgaaaata ttaatcatag aatagttgtt 12450 12500 gtatgctaag tcactgaccc atattatgta cagcatttct ttgcaagatt gatctttact agtgatacta tcccaataca ctgctggaga tggagaaata 12550 12600 aatcagaatt agttgtccaa tagtaaatta ggcaagaaga taagtacaag tgtaatatgg acagtatcta acttgaaaag atttcaggcg 12650 aaaagaatct ggggtttgcc agtcagttgc tcaaaaggtc aatgaaaacc 12700 aaatagtgaa gctatcagag aagctaataa attatagact gcttgaacag 12750 ttgtgtccag attaagggag ataatagctt tcccacccta ctttgtgcag 12800 gtcatacctc cccaaagtgt ttacctaatc agtaggttca caaactcttg 12850 gtcattatag tatatgccta aaatgtatgc acttaggaat gctaaaaatt 12900 taaatatggt ctaaagcaaa taaaagcaaa gaggaaaaac tttggacagc 12950 gaatagtctt gtaaagacta agccagtata ttaaaaagaa ttggtttgaa 13000 atatagagat gtgtcccaat ttcaagtatt ttaattgcac cttaatgaaa 13050 ttatctattt tctatagatt ttagtactat tgaatgtatt actttactgt 13100 tacctgaatt tattataaag tgtttttgaa taaataattc taaaagc 13147

<210> 4 <210> 4

<211> 8228 <211> 8228

<212> ADN <212> DNA

<213> Homo sapiens <213> Homo sapiens

<400> 4<400> 4

gcctccacac ggctccgtcg ggcgccgcgc tcttccggca gcggtagctt 50 tggagacgcc gggaacccgc gttggcgtgg ttgactagtg cctcgcagcc 100 tcagcatggg ggaacatggc ctggagctgg cttccatgat ccccgccctg 150 cgggagctgg gcagtgccac accagaggaa tataatacag ttgtacagaa 200 gccaagacaa attctgtgtc aattcattga ccggatactt acagatgtaa 250 atgttgttgc tgtagaactt gtaaagaaaa ctgactctca gccaacctcc 300 gtgatgttgc ttgatttcat ccagcatatc atgaaatcct ccccacttat 350 gtttgtaaat gtgagtggaa gccatgaggc caaaggcagt tgtattgaat 400 tcagtaattg gatcataacg agacttctgc ggattgcagc aactccctcc 450 tgtcatttgt tacacaagaa aatctgtgaa gtcatctgtt cattattatt 500 tctttttaaa agcaagagtc ctgctatttt tggggtactc acaaaagaat 550 tattacaact ttttgaagac ttggtttacc tccatagaag aaatgtgatg 600 ggtcatgctg tggaatggcc agtggtcatg agccgatttt taagtcaatt 650 agatgaacac atgggatatt tacaatcagc tcctttgcag ttgatgagta 700 tgcaaaattt agaatttatt gaagtcactt tattaatggt tcttactcgt 750 attattgcaa ttgtgttttt tagaaggcaa gaactcttac tttggcagat 800 aggttgtgtt ctgctagagt atggtagtcc aaaaattaaa tccctagcaa 850 ttagcttttt aacagaactt tttcagcttg gaggactacc agcacaacca 900 gctagcactt ttttcagctc atttttggaa ttattaaaac accttgtaga 950 aatggatact gaccaattga aactctatga agagccatta tcaaagctga 1000 taaagacact atttcccttt gaagcagaag cttatagaaa tattgaacct 1050 gtctatttaa atatgctgct ggaaaaactc tgtgtcatgt ttgaagacgg 1100 tgtgctcatg cggcttaagt ctgatttgct aaaagcagct ttgtgccatt 1150 tactgcagta tttccttaaa tttgtgccag ctgggtatga atctgcttta 1200 caagtcagga aggtctatgt gagaaatatt tgtaaagctc ttttggatgt 1250 gcttggaatt gaggtagatg cagagtactt gttgggccca ctttatgcag 1300 ctttgaaaat ggaaagtatg gaaatcattg aggagattca atgccaaact 1350 caacaggaaa acctcagcag taatagtgat ggaatatcac ccaaaaggcg 1400 tcgtctcagc tcgtctctaa acccttctaa aagagcacca aaacagactg 1450 aggaaattaa acatgtggac atgaaccaaa agagcatatt atggagtgca 1500 ctgaaacaga aagctgaatc ccttcagatt tcccttgaat acagtggcct 1550 aaagaatcct gttattgaga tgttagaagg aattgctgtt gtcttacaac 1600 tgactgctct gtgtactgtt cattgttctc atcaaaacat gaactgccgt 1650 actttcaagg actgtcaaca taaatccaag aagaaacctt ctgtagtgat 1700 aacttggatg tcattggatt tttacacaaa agtgcttaag agctgtagaa 1750 gtttgttaga atctgttcag aaactggacc tggaggcaac cattgataag 1800 gtggtgaaaa tttatgatgc tttgatttat atgcaagtaa acagttcatt 1850 tgaagatcat atcctggaag atttatgtgg tatgctctca cttccatgga 1900 tttattccca ttctgatgat ggctgtttaa agttgaccac atttgccgct 1950 aatcttctaa cattaagctg taggatttca gatagctatt caccacaggc 2000 acaatcacga tgtgtgtttc ttctgactct gtttccaaga agaatattcc 2050 ttgagtggag aacagcagtt tacaactggg ccctgcagag ctcccatgaa 2100 gtaatccggg ctagttgtgt tagtggattt tttatcttat tgcagcagca 2150 gaattcttgt aacagagttc ccaagattct tatagataaa gtcaaagatg 2200 attctgacat tgtcaagaaa gaatttgctt ctatacttgg tcaacttgtc 2250 tgtactcttc acggcatgtt ttatctgaca agttctttaa cagaaccttt 2300 ctctgaacac ggacatgtgg acctcttctg taggaacttg aaagccactt 2350 ctcaacatga atgttcatct tctcaactaa aagcttctgt ctgcaagcca 2400 ttccttttcc tactgaaaaa aaaaatacct agtccagtaa aacttgcttt 2450 catagataat ctacatcatc tttgtaagca tcttgatttt agagaagatg 2500 aaacagatgt aaaagcagtt cttggaactt tattaaattt aatggaagat 2550 ccagacaaag atgttagagt ggcttttagt ggaaatatca agcacatatt 2600 ggaatccttg gactctgaag atggatttat aaaggagctt tttgtcttaa 2650 gaatgaagga agcatataca catgcccaaa tatcaagaaa taatgagctg 2700 aaggatacct tgattcttac aacaggggat attggaaggg ccgcaaaagg 2750 agatttggta ccatttgcac tcttacactt attgcattgt ttgttatcca 2800 agtcagcatc tgtctctgga gcagcataca cagaaattag agctctggtt 2850 gcagctaaaa gtgttaaact gcaaagtttt ttcagccagt ataagaaacc 2900 catctgtcag tttttggtag aatcccttca ctctagtcag atgacagcac 2950 ttccgaatac tccatgccag aatgctgacg tgcgaaaaca agatgtggct 3000 caccagagag aaatggcttt aaatacgttg tctgaaattg ccaacgtttt 3050 cgactttcct gatcttaatc gttttcttac taggacatta caagttctac 3100 tacctgatct tgctgccaaa gcaagccctg cagcttctgc tctcattcga 3150 actttaggaa aacaattaaa tgtcaatcgt agagagattt taataaacaa 3200 cttcaaatat attttttctc atttggtctg ttcttgttcc aaagatgaat 3250 tagaacgtgc ccttcattat ctgaagaatg aaacagaaat tgaactgggg 3300 agcctgttga gacaagattt ccaaggattg cataatgaat tattgctgcg 3350 tattggagaa cactatcaac aggtttttaa tggtttgtca atacttgcct 3400 catttgcatc cagtgatgat ccatatcagg gcccgagaga tatcatatca 3450 cctgaactga tggctgatta tttacaaccc aaattgttgg gcattttggc 3500 tttttttaac atgcagttac tgagctctag tgttggcatt gaagataaga 3550 aaatggcctt gaacagtttg atgtctttga tgaagttaat gggacccaaa 3600 catgtcagtt ctgtgagggt gaagatgatg accacactga gaactggcct 3650 tcgattcaag gatgattttc ctgaattgtg ttgcagagct tgggactgct 3700 ttgttcgctg cctggatcat gcttgtctgg gctcccttct cagtcatgta 3750 atagtagctt tgttacctct tatacacatc cagcctaaag aaactgcagc 3800 tatcttccac tacctcataa ttgaaaacag ggatgctgtg caagattttc 3850 ttcatgaaat atatttttta cctgatcatc cagaattaaa aaagataaaa 3900 gccgttctcc aggaatacag aaaggagacc tctgagagca ctgatcttca 3950 gacaactctt cagctctcta tgaaggccat tcaacatgaa aatgtcgatg 4000 ttcgtattca tgctcttaca agcttgaagg aaaccttgta taaaaatcag 4050 gaaaaactga taaagtatgc aacagacagt gaaacagtag aacctattat 4100 ctcacagttg gtgacagtgc ttttgaaagg ttgccaagat gcaaactctc 4150 aagctcggtt gctctgtggg gaatgtttag gggaattggg ggcgatagat 4200 ccaggtcgat tagatttctc aacaactgaa actcaaggaa aagattttac 4250 atttgtgact ggagtagaag attcaagctt tgcctatgga ttattgatgg 4300 agctaacaag agcttacctt gcgtatgctg ataatagccg agctcaagat 4350 tcagctgcct atgccattca ggagttgctt tctatttatg actgtagaga 4400 gatggagacc aacggcccag gtcaccaatt gtggaggaga tttcctgagc 4450 atgttcggga aatactagaa cctcatctaa ataccagata caagagttct 4500 cagaagtcaa ccgattggtc tggagtaaag aagccaattt acttaagtaa 4550 attgggtagt aactttgcag aatggtcagc atcttgggca ggttatctta 4600 ttacaaaggt tcgacatgat cttgccagta aaattttcac ctgctgtagc 4650 attatgatga agcatgattt caaagtgacc atctatcttc ttccacatat 4700 tctggtgtat gtcttactgg gttgtaatca agaagatcag caggaggttt 4750 atgcagaaat tatggcagtt ctaaagcatg acgatcagca taccataaat 4800 acccaagaca ttgcatctga tctgtgtcaa ctcagtacac agactgtgtt 4850 ctccatgctt gaccatctca cacagtgggc aaggcacaaa tttcaggcac 4900 tgaaagctga gaaatgtcca cacagcaaat caaacagaaa taaggtagac 4950 tcaatggtat ctactgtgga ttatgaagac tatcagagtg taacccgttt 5000 tctagacctc ataccccagg atactctggc agtagcttcc tttcgctcca 5050 aagcatacac acgagctgta atgcactttg aatcatttat tacagaaaag 5100 aagcaaaata ttcaggaaca tcttggattt ttacagaaat tgtatgctgc 5150 tatgcatgaa cctgatggag tggccggagt cagtgcaatt agaaaggcag 5200 aaccatctct aaaagaacag atccttgaac atgaaagcct tggcttgctg 5250 agggatgcca ctgcttgtta tgacagggct attcagctag aaccagacca 5300 gatcattcat tatcatggtg tagtaaagtc catgttaggt cttggtcagc 5350 tgtctactgt tatcactcag gtgaatggag tgcatgctaa caggtccgag 5400 tggacagatg aattaaacac gtacagagtg gaagcagctt ggaaattgtc 5450 acagtgggat ttggtggaaa actatttggc agcagatgga aaatctacaa 5500 catggagtgt cagactggga cagctattat tatcagccaa aaaaagagat 5550 atcacagctt tttatgactc actgaaacta gtgagagcag aacaaattgt 5600 acctctttca gctgcaagct ttgaaagagg ctcctaccaa cgaggatatg 5650 aatatattgt gagattgcac atgttatgtg agttggagca tagcatcaaa 5700 ccacttttcc agcattctcc aggtgacagt tctcaagaag attctctaaa 5750 ctgggtagct cgactagaaa tgacccagaa ttcctacaga gccaaggagc 5800 ctatcctggc tctccggagg gctttactaa gcctcaacaa aagaccagat 5850 tacaatgaaa tggttggaga atgctggctg cagagtgcca gggtagctag 5900 aaaggctggt caccaccaga cagcctacaa tgctctcctt aatgcagggg 5950 aatcacgact cgctgaactg tacgtggaaa gggcaaagtg gctctggtcc 6000 aagggtgatg ttcaccaggc actaattgtt cttcaaaaag gtgttgaatt 6050 atgttttcct gaaaatgaaa ccccacctga gggtaagaac atgttaatcc 6100 atggtcgagc tatgctacta gtgggccgat ttatggaaga aacagctaac 6150 tttgaaagca atgcaattat gaaaaaatat aaggatgtga ccgcgtgcct 6200 gccagaatgg gaggatgggc atttttacct tgccaagtac tatgacaaat 6250 tgatgcccat ggtcacagac aacaaaatgg aaaagcaagg tgatctcatc 6300 cggtatatag ttcttcattt tggcagatct ctacaatatg gaaatcagtt 6350 catatatcag tcaatgccac gaatgttaac tctatggctt gattatggta 6400 caaaggcata tgaatgggaa aaagctggcc gctccgatcg tgtacaaatg 6450 aggaatgatt tgggtaaaat aaacaaggtt atcacagagc atacaaacta 6500 tttagctcca tatcaatttt tgactgcttt ttcacaattg atctctcgaa 6550 tttgtcattc tcacgatgaa gtttttgttg tcttgatgga aataatagcc 6600 aaagtatttc tagcctatcc tcaacaagca atgtggatga tgacagctgt 6650 gtcaaagtca tcttatccca tgcgtgtgaa cagatgcaag gaaatcctca 6700 ataaagctat tcatatgaaa aaatccttag agaagtttgt tggagatgca 6750 actcgcctaa cagataagct tctagaattg tgcaataaac cggttgatgg 6800 aagtagttcc acattaagca tgagcactca ttttaaaatg cttaaaaagc 6850 tggtagaaga agcaacattt agtgaaatcc tcattcctct acaatcagtc 6900 atgataccta cacttccatc aattctgggt acccatgcta accatgctag 6950 ccatgaacca tttcctggac attgggccta tattgcaggg tttgatgata 7000 tggtggaaat tcttgcttct cttcagaaac caaagaagat ttctttaaaa 7050 ggctcagatg gaaagttcta catcatgatg tgtaagccaa aagatgacct 7100 gagaaaggat tgtagactaa tggaattcaa ttccttgatt aataagtgct 7150 taagaaaaga tgcagagtct cgtagaagag aacttcatat tcgaacatat 7200 gcagttattc cactaaatga tgaatgtggg attattgaat gggtgaacaa 7250 cactgctggt ttgagaccta ttctgaccaa actatataaa gaaaagggag 7300 tgtatatgac aggaaaagaa cttcgccagt gtatgctacc aaagtcagca 7350 gctttatctg aaaaactcaa agtattccga gaatttctcc tgcccaggca 7400 tcctcctatt tttcatgagt ggtttctgag aacattccct gatcctacat 7450 catggtacag tagtagatca gcttactgcc gttccactgc agtaatgtca 7500 atggttggtt atattctggg gcttggagac cgtcatggtg aaaatattct 7550 ctttgattct ttgactggtg aatgcgtaca tgtagatttc aattgtcttt 7600 tcaataaggg agaaaccttt gaagttccag aaattgtgcc atttcgcctg 7650 actcataata tggttaatgg aatgggtcct atgggaacag agggtctttt 7700 tcgaagagca tgtgaagtta caatgaggct gatgcgtgat cagcgagagc 7750 ctttaatgag tgtcttaaag acttttctac atgatcctct tgtggaatgg 7800 agtaaaccag tgaaagggca ttccaaagcg ccactgaatg aaactggaga 7850 agttgtcaat gaaaaggcca agacccatgt tcttgacatt gagcagcgac 7900 tacaaggtgt aatcaagact cgaaatagag tgacaggact gccgttatct 7950 attgaaggac atgtgcatta ccttatacag gaagctactg atgaaaactt 8000 actatgccag atgtatcttg gttggactcc atatatgtga aatgaaatta 8050 tgtaaaagaa tatgttaata atctaaaagt aatgcatttg gtatgaatct 8100 gtggttgtat ctgttcaatt ctaaagtaca acataaattt acgttctcag 8150 caactgttat ttctctctga tcattaatta tatgtaaaat aatatacatt 8200 cagttattaa gaaataaact gctttctt 8228 gcctccacac ggctccgtcg ggcgccgcgc tcttccggca gcggtagctt 50 tggagacgcc gggaacccgc gttggcgtgg ttgactagtg cctcgcagcc 100 tcagcatggg ggaacatggc ctggagctgg cttccatgat ccccgccctg 150 cgggagctgg gcagtgccac accagaggaa tataatacag ttgtacagaa 200 attctgtgtc gccaagacaa ccggatactt aattcattga acagatgtaa 250 atgttgttgc tgtagaactt gtaaagaaaa ctgactctca gccaacctcc 300 gtgatgttgc ttgatttcat ccagcatatc atgaaatcct ccccacttat 350 gtttgtaaat gtgagtggaa gccatgaggc caaaggcagt tgtattgaat 400 tcagtaattg gatcataacg agacttctgc ggattgcagc aactccctcc 450 tgtcatttgt tacacaagaa aatctgtgaa gtcatctgtt cattattatt 500 tctttttaaa agcaagagtc ctgctatttt tggggtactc acaaaagaat 550 tattacaact ttttgaagac ttggtttacc tccatagaag aaatgtgatg 600 ggtcatgctg tggaatggcc agtggtcatg agccgatttt taagtcaatt 650 agatgaacac atgggatatt tacaatcagc tcctttgcag ttgatgagta 700 tgcaaaattt agaatttatt gaagtcactt tattaatggt tcttactcgt 750 attattgcaa ttgtgttttt tagaaggcaa gaactcttac tttggcagat 800 aggttgtgtt ctgctagagt atggtagtcc aaaaatta aa tccctagcaa 850 ttagcttttt aacagaactt tttcagcttg gaggactacc agcacaacca 900 gctagcactt ttttcagctc atttttggaa ttattaaaac accttgtaga 950 aatggatact gaccaattga agagccatta aactctatga tcaaagctga 1000 taaagacact atttcccttt gaagcagaag cttatagaaa tattgaacct 1050 gtctatttaa atatgctgct ggaaaaactc tgtgtcatgt ttgaagacgg 1100 tgtgctcatg cggcttaagt ctgatttgct aaaagcagct ttgtgccatt 1150 tttccttaaa tactgcagta tttgtgccag atctgcttta ctgggtatga 1200 caagtcagga aggtctatgt gagaaatatt tgtaaagctc ttttggatgt 1250 gcttggaatt gaggtagatg cagagtactt gttgggccca ctttatgcag 1300 ctttgaaaat ggaaagtatg gaaatcattg aggagattca atgccaaact 1350 caacaggaaa acctcagcag taatagtgat ggaatatcac ccaaaaggcg 1400 tcgtctctaa tcgtctcagc acccttctaa aagagcacca aaacagactg 1450 aggaaattaa atgaaccaaa acatgtggac agagcatatt atggagtgca 1500 ctgaaacaga aagctgaatc ccttcagatt tcccttgaat acagtggcct 1550 aaagaatcct gttattgaga tgttagaagg aattgctgtt gtcttacaac 1600 tgactgctct gtgtactgtt cattgttctc atcaaaacat gaactgccgt 1650 actttca agg actgtcaaca taaatccaag aagaaacctt ctgtagtgat 1700 aacttggatg tcattggatt tttacacaaa agtgcttaag agctgtagaa 1750 gtttgttaga atctgttcag aaactggacc tggaggcaac cattgataag 1800 gtggtgaaaa tttatgatgc tttgatttat atgcaagtaa acagttcatt 1850 tgaagatcat atcctggaag atttatgtgg tatgctctca cttccatgga 1900 tttattccca ttctgatgat ggctgtttaa agttgaccac atttgccgct 1950 aatcttctaa cattaagctg taggatttca gatagctatt caccacaggc 2000 acaatcacga tgtgtgtttc ttctgactct gtttccaaga agaatattcc 2050 ttgagtggag aacagcagtt tacaactggg ccctgcagag ctcccatgaa 2100 gtaatccggg ctagttgtgt tagtggattt tttatcttat tgcagcagca 2150 gaattcttgt aacagagttc ccaagattct tatagataaa gtcaaagatg 2200 attctgacat tgtcaagaaa gaatttgctt ctatacttgg tcaacttgtc 2250 tgtactcttc acggcatgtt ttatctgaca agttctttaa cagaaccttt 2300 ctctgaacac ggacatgtgg acctcttctg taggaacttg aaagccactt 2350 atgttcatct ctcaacatga aagcttctgt tctcaactaa ctgcaagcca 2400 ttccttttcc tactgaaaaa aaaaatacct agtccagtaa aacttgcttt 2450 catagataat ctacatcatc tttgtaagc to tcttgatttt agagaagatg 2500 aaacagatgt aaaagcagtt cttggaactt tattaaattt aatggaagat 2550 ccagacaaag atgttagagt ggcttttagt ggaaatatca agcacatatt 2600 ggaatccttg gactctgaag atggatttat aaaggagctt tttgtcttaa 2650 agcatataca gaatgaagga tatcaagaaa catgcccaaa taatgagctg 2700 aaggatacct tgattcttac aacaggggat attggaaggg ccgcaaaagg 2750 agatttggta ccatttgcac tcttacactt attgcattgt ttgttatcca 2800 tgtctctgga agtcagcatc gcagcataca cagaaattag agctctggtt 2850 gcagctaaaa gtgttaaact gcaaagtttt ttcagccagt ataagaaacc 2900 catctgtcag tttttggtag aatcccttca ctctagtcag atgacagcac 2950 ttccgaatac tccatgccag aatgctgacg tgcgaaaaca agatgtggct 3000 caccagagag aaatggcttt aaatacgttg tctgaaattg ccaacgtttt 3050 cgactttcct gatcttaatc gttttcttac taggacatta caagttctac 3100 tacctgatct tgctgccaaa gcaagccctg cagcttctgc tctcattcga 3150 aacaattaaa actttaggaa tgtcaatcgt agagagattt taataaacaa 3200 cttcaaatat attttttctc atttggtctg ttcttgttcc aaagatgaat 3250 tagaacgtgc ccttcattat ctgaagaatg aaacagaaat tgaactgggg 3300 agcctgttga gacaagattt ccaaggattg cataatgaat tattgctgcg 3350 tattggagaa cactatcaac aggtttttaa tggtttgtca atacttgcct 3400 catttgcatc cagtgatgat ccatatcagg tatcatatca gcccgagaga 3450 tggctgatta cctgaactga tttacaaccc aaattgttgg gcattttggc 3500 tttttttaac atgcagttac tgagctctag tgttggcatt gaagataaga 3550 aaatggcctt gaacagtttg atgtctttga tgaagttaat gggacccaaa 3600 catgtcagtt ctgtgagggt gaagatgatg accacactga gaactggcct 3650 tcgattcaag gatgattttc ctgaattgtg ttgcagagct tgggactgct 3700 ttgttcgctg cctggatcat gcttgtctgg gctcccttct cagtcatgta 3750 atagtagctt tgttacctct tatacacatc cagcctaaag aaactgcagc 3800 tatcttccac tacctcataa ttgaaaacag ggatgctgtg caagattttc 3850 ttcatgaaat atatttttta cctgatcatc cagaattaaa aaagataaaa 3900 gccgttctcc aggaatacag aaaggagacc tctgagagca ctgatcttca 3950 cagctctcta gacaactctt tgaaggccat tcaacatgaa aatgtcgatg 4000 tgctcttaca ttcgtattca agcttgaagg aaaccttgta taaaaatcag 4050 gaaaaactga taaagtatgc aacagacagt gaaacagtag aacctattat 4100 ctcacagttg gtgacag tgc ttttgaaagg ttgccaagat gcaaactctc 4150 aagctcggtt gctctgtggg gaatgtttag gggaattggg ggcgatagat 4200 ccaggtcgat tagatttctc aacaactgaa actcaaggaa aagattttac 4250 atttgtgact ggagtagaag attcaagctt tgcctatgga ttattgatgg 4300 agctaacaag agcttacctt gcgtatgctg ataatagccg agctcaagat 4350 tcagctgcct atgccattca ggagttgctt tctatttatg actgtagaga 4400 gatggagacc aacggcccag gtcaccaatt gtggaggaga tttcctgagc 4450 aatactagaa atgttcggga ataccagata cctcatctaa caagagttct 4500 cagaagtcaa ccgattggtc tggagtaaag aagccaattt acttaagtaa 4550 attgggtagt aactttgcag aatggtcagc atcttgggca ggttatctta 4600 ttacaaaggt tcgacatgat cttgccagta aaattttcac ctgctgtagc 4650 attatgatga agcatgattt caaagtgacc atctatcttc ttccacatat 4700 tctggtgtat gtcttactgg gttgtaatca agaagatcag caggaggttt 4750 atgcagaaat tatggcagtt ctaaagcatg acgatcagca taccataaat 4800 ttgcatctga acccaagaca tctgtgtcaa ctcagtacac agactgtgtt 4850 gaccatctca ctccatgctt cacagtgggc aaggcacaaa tttcaggcac 4900 gaaatgtcca tgaaagctga cacagcaaat caaacagaa to taaggtagac 4950 tcaatggtat ctactgtgga ttatgaagac tatcagagtg taacccgttt 5000 tctagacctc ataccccagg atactctggc agtagcttcc tttcgctcca 5050 aagcatacac acgagctgta atgcactttg aatcatttat tacagaaaag 5100 ttcaggaaca aagcaaaata tcttggattt ttacagaaat tgtatgctgc 5150 tatgcatgaa cctgatggag tggccggagt cagtgcaatt agaaaggcag 5200 aaccatctct aaaagaacag atccttgaac atgaaagcct tggcttgctg 5250 ctgcttgtta agggatgcca tgacagggct attcagctag aaccagacca 5300 gatcattcat tatcatggtg tagtaaagtc catgttaggt cttggtcagc 5350 tgtctactgt tatcactcag gtgaatggag tgcatgctaa caggtccgag 5400 tggacagatg aattaaacac gtacagagtg gaagcagctt ggaaattgtc 5450 ttggtggaaa acagtgggat agcagatgga actatttggc aaatctacaa 5500 cagactggga catggagtgt cagctattat tatcagccaa aaaaagagat 5550 atcacagctt tttatgactc actgaaacta gtgagagcag aacaaattgt 5600 acctctttca gctgcaagct ttgaaagagg ctcctaccaa cgaggatatg 5650 aatatattgt gagattgcac atgttatgtg agttggagca tagcatcaaa 5700 ccacttttcc agcattctcc aggtgacagt tctcaagaag attctctaaa 5750 ctggg tagct tgacccagaa cgactagaaa ttcctacaga gccaaggagc 5800 ctatcctggc tctccggagg gctttactaa gcctcaacaa aagaccagat 5850 tggttggaga tacaatgaaa cagagtgcca atgctggctg gggtagctag 5900 caccaccaga aaaggctggt cagcctacaa tgctctcctt aatgcagggg 5950 aatcacgact cgctgaactg tacgtggaaa gggcaaagtg gctctggtcc 6000 aagggtgatg ttcaccaggc actaattgtt cttcaaaaag gtgttgaatt 6050 gaaaatgaaa atgttttcct ccccacctga gggtaagaac atgttaatcc 6100 atggtcgagc tatgctacta gtgggccgat ttatggaaga aacagctaac 6150 tttgaaagca atgcaattat gaaaaaatat aaggatgtga ccgcgtgcct 6200 gccagaatgg gaggatgggc atttttacct tgccaagtac tatgacaaat 6250 tgatgcccat ggtcacagac aacaaaatgg aaaagcaagg tgatctcatc 6300 cggtatatag ttcttcattt tggcagatct ctacaatatg gaaatcagtt 6350 catatatcag tcaatgccac gaatgttaac tctatggctt gattatggta 6400 tgaatgggaa caaaggcata aaagctggcc gctccgatcg tgtacaaatg 6450 aggaatgatt tgggtaaaat aaacaaggtt atcacagagc atacaaacta 6500 tttagctcca tatcaatttt tgactgcttt ttcacaattg atctctcgaa 6550 tttgtcattc tcacgatgaa gtttttgt tg tcttgatgga aataatagcc 6600 aaagtatttc tagcctatcc tcaacaagca atgtggatga tgacagctgt 6650 tcttatccca gtcaaagtca tgcgtgtgaa gaaatcctca cagatgcaag 6700 ataaagctat tcatatgaaa aaatccttag agaagtttgt tggagatgca 6750 actcgcctaa cagataagct tctagaattg tgcaataaac cggttgatgg 6800 acattaagca aagtagttcc tgagcactca ttttaaaatg cttaaaaagc 6850 tggtagaaga agcaacattt agtgaaatcc tcattcctct acaatcagtc 6900 atgataccta cacttccatc aattctgggt acccatgcta accatgctag 6950 ccatgaacca tttcctggac attgggccta tattgcaggg tttgatgata 7000 tggtggaaat tcttgcttct cttcagaaac caaagaagat ttctttaaaa 7050 ggctcagatg gaaagttcta catcatgatg tgtaagccaa aagatgacct 7100 gagaaaggat tgtagactaa tggaattcaa ttccttgatt aataagtgct 7150 taagaaaaga tgcagagtct cgtagaagag aacttcatat tcgaacatat 7200 cactaaatga gcagttattc tgaatgtggg attattgaat gggtgaacaa 7250 ttgagaccta cactgctggt ttctgaccaa actatataaa gaaaagggag 7300 tgtatatgac aggaaaagaa cttcgccagt gtatgctacc aaagtcagca 7350 aaaaactcaa gctttatctg agtattccga gaatttctcc tgcccaggca 7400 tcctcctatt tttcatgagt ggtttctgag aacattccct gatcctacat 7450 catggtacag tagtagatca gcttactgcc gttccactgc agtaatgtca 7500 atggttggtt atattctggg gcttggagac cgtcatggtg aaaatattct 7550 ctttgattct ttgactggtg aatgcgtaca tgtagatttc aattgtcttt 7600 tcaataaggg agaaaccttt gaagttccag aaattgtgcc atttcgcctg 7650 actcataata tggttaatgg aatgggtcct atgggaacag agggtctttt 7700 tgtgaagtta tcgaagagca caatgaggct gatgcgtgat cagcgagagc 7750 ctttaatgag tgtcttaaag acttttctac atgatcctct tgtggaatgg 7800 agtaaaccag tgaaagggca ttccaaagcg ccactgaatg aaactggaga 7850 agttgtcaat gaaaaggcca agacccatgt tcttgacatt gagcagcgac 7900 tacaaggtgt aatcaagact cgaaatagag tgacaggact gccgttatct 7950 attgaaggac atgtgcatta ccttatacag gaagctactg atgaaaactt 8000 actatgccag atgtatcttg gttggactcc atatatgtga aatgaaatta 8050 tatgttaata tgtaaaagaa atctaaaagt aatgcatttg gtatgaatct 8100 gtggttgtat ctgttcaatt ctaaagtaca acataaattt acgttctcag 8150 ttctctctga caactgttat tcattaatta tatgtaaaat aatatacatt 8200 gaaataa cagttattaa act gctttctt 8228

<210> 5 <210> 5

<211> 3603 <211> 3603

<212> ADN <213> Homo sapiens <212> DNA <213> Homo sapiens

<400> 5 <400> 5

agtcaaggct ttgacagggc atagtctcct ccaataatct tctccgttct 50 agtcaaggct ttgacagggc atagtctcct ccaataatct tctccgttct 50

ctctcattat tccctcgagt tcttctcagt caagctgcat gtatgtatgt 100 ctctcattat tccctcgagt tcttctcagt caagctgcat gtatgtatgt 100

gtgtcccgag aagcggtttg atactgagct gcatttgcct ttactgtgga 150 gtgtcccgag aagcggtttg atactgagct gcatttgcct ttactgtgga 150

gttttgttgc cggttctgct ccctaatctt ccttttctga cgtgcctgag 200 gttttgttgc cggttctgct ccctaatctt ccttttctga cgtgcctgag 200

catgtccaca ttagaatctg tgacatacct acctgaaaaa ggtttatatt 250 catgtccaca ttagaatctg tgacatacct acctgaaaaa ggtttatatt 250

gtcagagact gccaagcagc cggacacacg ggggcacaga atcactgaag 300 gtcagagact gccaagcagc cggacacacg ggggcacaga atcactgaag 300

gggaaaaata cagaaaatat gggtttctac ggcacattaa aaatgatttt 350 gggaaaaata cagaaaatat gggtttctac ggcacattaa aaatgatttt 350

ttacaaaatg aaaagaaagt tggaccatgg ttctgaggtc cgctcttttt 400 ttacaaaatg aaaagaaagt tggaccatgg ttctgaggtc cgctcttttt 400

ctttgggaaa gaaaccatgc aaagtctcag aatatacaag taccactggg 450 ctttgggaaa gaaaccatgc aaagtctcag aatatacaag taccactggg 450

cttgtaccat gttcagcaac accaacaact tttggggacc tcagagcagc 500 cttgtaccat gttcagcaac accaacaact tttggggacc tcagagcagc 500

caatggccaa gggcaacaac gacgccgaat tacatctgtc cagccaccta 550 caatggccaa gggcaacaac gacgccgaat tacatctgtc cagccaccta 550

caggcctcca ggaatggcta aaaatgtttc agagctggag tggaccagag 600 caggcctcca ggaatggcta aaaatgtttc agagctggag tggaccagag 600

aaattgcttg ctttagatga actcattgat agttgtgaac caacacaagt 650 aaattgcttg ctttagatga actcattgat agttgtgaac caacacaagt 650

aaaacatatg atgcaagtga tagaacccca gtttcaacga gacttcattt 700 aaaacatatg atgcaagtga tagaacccca gtttcaacga gacttcattt 700

cattgctccc taaagagttg gcactctatg tgctttcatt cctggaaccc 750 cattgctccc taaagagttg gcactctatg tgctttcatt cctggaaccc 750

aaagacctgc tacaagcagc tcagacatgt cgctactgga gaattttggc 800 aaagacctgc tacaagcagc tcagacatgt cgctactgga gaattttggc 800

tgaagacaac cttctctgga gagagaaatg caaagaagag gggattgatg 850 tgaagacaac cttctctgga gagagaaatg caaagaagag gggattgatg 850

aaccattgca catcaagaga agaaaagtaa taaaaccagg tttcatacac 900 aaccattgca catcaagaga agaaaagtaa taaaaccagg tttcatacac 900

agtccatgga aaagtgcata catcagacag cacagaattg atactaactg 950 agtccatgga aaagtgcata catcagacag cacagaattg atactaactg 950

gaggcgagga gaactcaaat ctcctaaggt gctgaaagga catgatgatc 1000 gaggcgagga gaactcaaat ctcctaaggt gctgaaagga catgatgatc 1000

atgtgatcac atgcttacag ttttgtggta accgaatagt tagtggttct 1050 atgtgatcac atgcttacag ttttgtggta accgaatagt tagtggttct 1050

gatgacaaca ctttaaaagt ttggtcagca gtcacaggca aatgtctgag 1100 gatgacaaca ctttaaaagt ttggtcagca gtcacaggca aatgtctgag 1100

aacattagtg ggacatacag gtggagtatg gtcatcacaa atgagagaca 1150 aacattagtg ggacatacag gtggagtatg gtcatcacaa atgagagaca 1150

acatcatcat tagtggatct acagatcgga cactcaaagt gtggaatgca 1200 acatcatcat tagtggatct acagatcgga cactcaaagt gtggaatgca 1200

gagactggag aatgtataca caccttatat gggcatactt ccactgtgcg 1250 gagactggag aatgtataca caccttatat gggcatactt ccactgtgcg 1250

ttgtatgcat cttcatgaaa aaagagttgt tagcggttct cgagatgcca 1300 ttgtatgcat cttcatgaaa aaagagttgt tagcggttct cgagatgcca 1300

ctcttagggt ttgggatatt gagacaggcc agtgtttaca tgttttgatg 1350 ctcttagggt ttgggatatt gagacaggcc agtgtttaca tgttttgatg 1350

ggtcatgttg cagcagtccg ctgtgttcaa tatgatggca ggagggttgt 1400 ggtcatgttg cagcagtccg ctgtgttcaa tatgatggca ggagggttgt 1400

tagtggagca tatgatttta tggtaaaggt gtgggatcca gagactgaaa 1450 tagtggagca tatgatttta tggtaaaggt gtgggatcca gagactgaaa 1450

cctgtctaca cacgttgcag gggcatacta atagagtcta ttcattacag 1500 cctgtctaca cacgttgcag gggcatacta atagagtcta ttcattacag 1500

tttgatggta tccatgtggt gagtggatct cttgatacat caatccgtgt 1550 tttgatggta tccatgtggt gagtggatct cttgatacat caatccgtgt 1550

ttgggatgtg gagacaggga attgcattca cacgttaaca gggcaccagt 1600 ttgggatgtg gagacaggga attgcattca cacgttaaca gggcaccagt 1600

cgttaacaag tggaatggaa ctcaaagaca atattcttgt ctctgggaat 1650 cgttaacaag tggaatggaa ctcaaagaca atattcttgt ctctgggaat 1650

gcagattcta cagttaaaat ctgggatatc aaaacaggac agtgtttaca 1700 aacattgcaa ggtcccaaca agcatcagag tgctgtgacc tgtttacagt 1750 tcaacaagaa ctttgtaatt accagctcag atgatggaac tgtaaaacta 1800 tgggacttga aaacgggtga atttattcga aacctagtca cattggagag 1850 tggggggagt gggggagttg tgtggcggat cagagcctca aacacaaagc 1900 tggtgtgtgc agttgggagt cggaatggga ctgaagaaac caagctgctg 1950 gtgctggact ttgatgtgga catgaagtga agagcagaaa agatgaattt 2000 gtccaattgt gtagacgata tactccctgc ccttccccct gcaaaaagaa 2050 aaaaagaaaa gaaaaagaaa aaaatccctt gttctcagtg gtgcaggatg 2100 ttggcttggg gcaacagatt gaaaagacct acagactaag aaggaaaaga 2150 agaagagatg acaaaccata actgacaaga gaggcgtctg ctgtctcatc 2200 acataaaagg cttcactttt gactgagggc agctttgcaa aatgagactt 2250 tctaaatcaa accaggtgca attatttctt tattttcttc tccagtggtc 2300 attgggcagt gttaatgctg aaacatcatt acagattctg ctagcctgtt 2350 cttttaccac tgacagctag acacctagaa aggaactgca ataatatcaa 2400 aacaagtact ggttgacttt ctaattagag agcatctgca acaaaaagtc 2450 atttttctgg agtggaaaag cttaaaaaaa ttactgtgaa ttgtttttgt 2500 acagttatca tgaaaagctt tttttttttt ttttttgcca accattgcca 2550 atgtcaatca atcacagtat tagcctctgt taatctattt actgttgctt 2600 ccatatacat tcttcaatgc atatgttgct caaaggtggc aagttgtcct 2650 gggttctgtg agtcctgaga tggatttaat tcttgatgct ggtgctagaa 2700 gtaggtcttc aaatatggga ttgttgtccc aaccctgtac tgtactccca 2750 gtggccaaac ttatttatgc tgctaaatga aagaaagaaa aaagcaaatt 2800 attttttttt attttttttc tgctgtgacg ttttagtccc agactgaatt 2850 ccaaatttgc tctagtttgg ttatggaaaa aagacttttt gccactgaaa 2900 cttgagccat ctgtgcctct aagaggctga gaatggaaga gtttcagata 2950 ataaagagtg aagtttgcct gcaagtaaag aattgagagt gtgtgcaaag 3000 cttattttct tttatctggg caaaaattaa aacacattcc ttggaacaga 3050 gctattactt gcctgttctg tggagaaact tttctttttg agggctgtgg 3100 tgaatggatg aacgtacatc gtaaaactga caaaatattt taaaaatata 3150 taaaacacaa aattaaaata aagttgctgg tcagtcttag tgttttacag 3200 tatttgggaa aacaactgtt acagttttat tgctctgagt aactgacaaa 3250 gcagaaacta ttcagttttt gtagtaaagg cgtcacatgc aaacaaacaa 3300 aatgaatgaa acagtcaaat ggtttgcctc attctccaag agccacaact 3350 caagctgaac tgtgaaagtg gtttaacact gtatcctagg cgatcttttt 3400 tcctccttct gtttattttt ttgtttgttt tatttatagt ctgatttaaa 3450 acaatcagat tcaagttggt taattttagt tatgtaacaa cctgacatga 3500 tggaggaaaa caacctttaa agggattgtg tctatggttt gattcactta 3550 gaaattttat tttcttataa cttaagtgca ataaaatgtg ttttttcatg 3600 tta 3603 gcagattcta cagttaaaat ctgggatatc aaaacaggac agtgtttaca 1700 ggtcccaaca aacattgcaa agcatcagag tgctgtgacc tgtttacagt 1750 tcaacaagaa ctttgtaatt accagctcag atgatggaac tgtaaaacta 1800 aaacgggtga tgggacttga atttattcga aacctagtca cattggagag 1850 tggggggagt gggggagttg tgtggcggat cagagcctca aacacaaagc 1900 tggtgtgtgc agttgggagt cggaatggga ctgaagaaac caagctgctg 1950 ttgatgtgga gtgctggact catgaagtga agagcagaaa agatgaattt 2000 gtccaattgt gtagacgata tactccctgc ccttccccct gcaaaaagaa 2050 gaaaaagaaa aaaaagaaaa aaaatccctt gttctcagtg gtgcaggatg 2100 ttggcttggg gcaacagatt gaaaagacct acagactaag aaggaaaaga 2150 agaagagatg acaaaccata actgacaaga gaggcgtctg ctgtctcatc 2200 acataaaagg cttcactttt gactgagggc agctttgcaa aatgagactt 2250 accaggtgca tctaaatcaa attatttctt tattttcttc tccagtggtc 2300 attgggcagt gttaatgctg aaacatcatt acagattctg ctagcctgtt 2350 cttttaccac tgacagctag aggaactgca acacctagaa ataatatcaa 2400 aacaagtact ggttgacttt ctaattagag agcatctgca acaaaaagtc 2450 atttttctgg agtggaaaag ct taaaaaaa ttactgtgaa ttgtttttgt 2500 tgaaaagctt acagttatca ttttttgcca tttttttttt accattgcca 2550 atgtcaatca atcacagtat tagcctctgt taatctattt actgttgctt 2600 ccatatacat tcttcaatgc atatgttgct caaaggtggc aagttgtcct 2650 gggttctgtg agtcctgaga tggatttaat tcttgatgct ggtgctagaa 2700 aaatatggga gtaggtcttc ttgttgtccc aaccctgtac tgtactccca 2750 gtggccaaac ttatttatgc tgctaaatga aagaaagaaa aaagcaaatt 2800 attttttttt attttttttc tgctgtgacg ttttagtccc agactgaatt 2850 ccaaatttgc tctagtttgg ttatggaaaa aagacttttt gccactgaaa 2900 cttgagccat ctgtgcctct aagaggctga gtttcagata gaatggaaga 2950 ataaagagtg aagtttgcct gcaagtaaag aattgagagt gtgtgcaaag 3000 cttattttct tttatctggg caaaaattaa aacacattcc ttggaacaga 3050 gctattactt gcctgttctg tggagaaact tttctttttg agggctgtgg 3100 tgaatggatg aacgtacatc gtaaaactga caaaatattt taaaaatata 3150 aattaaaata taaaacacaa aagttgctgg tcagtcttag tgttttacag 3200 tatttgggaa aacaactgtt acagttttat tgctctgagt aactgacaaa 3250 gcagaaacta ttcagttttt gtagtaaagg cgtcacatgc aaaca aacaa 3300 aatgaatgaa acagtcaaat ggtttgcctc attctccaag agccacaact 3350 caagctgaac tgtgaaagtg gtttaacact gtatcctagg cgatcttttt 3400 tcctccttct gtttattttt ttgtttgttt tatttatagt ctgatttaaa 3450 acaatcagat tcaagttggt taattttagt tatgtaacaa cctgacatga 3500 caacctttaa tggaggaaaa agggattgtg tctatggttt gattcactta 3550 tttcttataa gaaattttat cttaagtgca ataaaatgtg ttttttcatg 3600 3603 tta

<210> 6 <210> 6

<211> 5783 <211> 5783

<212> ADN <212> DNA

<213> Homo sapiens <213> Homo sapiens

<400> 6 <400> 6

gcggacactc ctctcggctc ctccccggca gcggcggcgg ctcggagcgg 50 gcggacactc ctctcggctc ctccccggca gcggcggcgg ctcggagcgg 50

gctccggggc tcgggtgcag cggccagcgg gcgcctggcg gcgaggatta 100 gctccggggc tcgggtgcag cggccagcgg gcgcctggcg gcgaggatta 100

cccggggaag tggttgtctc ctggctggag ccgcgagacg ggcgctcagg 150 cccggggaag tggttgtctc ctggctggag ccgcgagacg ggcgctcagg 150

gcgcggggcc ggcggcggcg aacgagagga cggactctgg cggccgggtc 200 gcgcggggcc ggcggcggcg aacgagagga cggactctgg cggccgggtc 200

gttggccgcg gggagcgcgg gcaccgggcg agcaggccgc gtcgcgctca 250 gttggccgcg gggagcgcgg gcaccgggcg agcaggccgc gtcgcgctca 250

ccatggtcag ctactgggac accggggtcc tgctgtgcgc gctgctcagc 300 ccatggtcag ctactgggac accggggtcc tgctgtgcgc gctgctcagc 300

tgtctgcttc tcacaggatc tagttcaggt tcaaaattaa aagatcctga 350 tgtctgcttc tcacaggatc tagttcaggt tcaaaattaa aagatcctga 350

actgagttta aaaggcaccc agcacatcat gcaagcaggc cagacactgc 400 actgagttta aaaggcaccc agcacatcat gcaagcaggc cagacactgc 400

atctccaatg caggggggaa gcagcccata aatggtcttt gcctgaaatg 450 atctccaatg caggggggaa gcagcccata aatggtcttt gcctgaaatg 450

gtgagtaagg aaagcgaaag gctgagcata actaaatctg cctgtggaag 500 gtgagtaagg aaagcgaaag gctgagcata actaaatctg cctgtggaag 500

aaatggcaaa caattctgca gtactttaac cttgaacaca gctcaagcaa 550 aaatggcaaa caattctgca gtactttaac cttgaacaca gctcaagcaa 550

accacactgg cttctacagc tgcaaatatc tagctgtacc tacttcaaag 600 accacactgg cttctacagc tgcaaatatc tagctgtacc tacttcaaag 600

aagaaggaaa cagaatctgc aatctatata tttattagtg atacaggtag 650 aagaaggaaa cagaatctgc aatctatata tttattagtg atacaggtag 650

acctttcgta gagatgtaca gtgaaatccc cgaaattata cacatgactg 700 acctttcgta gagatgtaca gtgaaatccc cgaaattata cacatgactg 700

aaggaaggga gctcgtcatt ccctgccggg ttacgtcacc taacatcact 750 aaggaaggga gctcgtcatt ccctgccggg ttacgtcacc taacatcact 750

gttactttaa aaaagtttcc acttgacact ttgatccctg atggaaaacg 800 gttactttaa aaaagtttcc acttgacact ttgatccctg atggaaaacg 800

cataatctgg gacagtagaa agggcttcat catatcaaat gcaacgtaca 850 cataatctgg gacagtagaa agggcttcat catatcaaat gcaacgtaca 850

aagaaatagg gcttctgacc tgtgaagcaa cagtcaatgg gcatttgtat 900 aagaaatagg gcttctgacc tgtgaagcaa cagtcaatgg gcatttgtat 900

aagacaaact atctcacaca tcgacaaacc aatacaatca tagatgtcca 950 aagacaaact atctcacaca tcgacaaacc aatacaatca tagatgtcca 950

aataagcaca ccacgcccag tcaaattact tagaggccat actcttgtcc 1000 aataagcaca ccacgcccag tcaaattact tagaggccat actcttgtcc 1000

tcaattgtac tgctaccact cccttgaaca cgagagttca aatgacctgg 1050 tcaattgtac tgctaccact cccttgaaca cgagagttca aatgacctgg 1050

agttaccctg atgaaaaaaa taagagagct tccgtaaggc gacgaattga 1100 agttaccctg atgaaaaaaa taagagagct tccgtaaggc gacgaattga 1100

ccaaagcaat tcccatgcca acatattcta cagtgttctt actattgaca 1150 ccaaagcaat tcccatgcca acatattcta cagtgttctt actattgaca 1150

aaatgcagaa caaagacaaa ggactttata cttgtcgtgt aaggagtgga 1200 aaatgcagaa caaagacaaa ggactttata cttgtcgtgt aaggagtgga 1200

ccatcattca aatctgttaa cacctcagtg catatatatg ataaagcatt 1250 catcactgtg aaacatcgaa aacagcaggt gcttgaaacc gtagctggca 1300 agcggtctta ccggctctct atgaaagtga aggcatttcc ctcgccggaa 1350 gttgtatggt taaaagatgg gttacctgcg actgagaaat ctgctcgcta 1400 tttgactcgt ggctactcgt taattatcaa ggacgtaact gaagaggatg 1450 cagggaatta tacaatcttg ctgagcataa aacagtcaaa tgtgtttaaa 1500 aacctcactg ccactctaat tgtcaatgtg aaaccccaga tttacgaaaa 1550 ggccgtgtca tcgtttccag acccggctct ctacccactg ggcagcagac 1600 aaatcctgac ttgtaccgca tatggtatcc ctcaacctac aatcaagtgg 1650 ttctggcacc cctgtaacca taatcattcc gaagcaaggt gtgacttttg 1700 ttccaataat gaagagtcct ttatcctgga tgctgacagc aacatgggaa 1750 acagaattga gagcatcact cagcgcatgg caataataga aggaaagaat 1800 aagatggcta gcaccttggt tgtggctgac tctagaattt ctggaatcta 1850 catttgcata gcttccaata aagttgggac tgtgggaaga aacataagct 1900 tttatatcac agatgtgcca aatgggtttc atgttaactt ggaaaaaatg 1950 ccgacggaag gagaggacct gaaactgtct tgcacagtta acaagttctt 2000 atacagagac gttacttgga ttttactgcg gacagttaat aacagaacaa 2050 tgcactacag tattagcaag caaaaaatgg ccatcactaa ggagcactcc 2100 atcactctta atcttaccat catgaatgtt tccctgcaag attcaggcac 2150 ctatgcctgc agagccagga atgtatacac aggggaagaa atcctccaga 2200 agaaagaaat tacaatcaga gatcaggaag caccatacct cctgcgaaac 2250 ctcagtgatc acacagtggc catcagcagt tccaccactt tagactgtca 2300 tgctaatggt gtccccgagc ctcagatcac ttggtttaaa aacaaccaca 2350 aaatacaaca agagcctgga attattttag gaccaggaag cagcacgctg 2400 tttattgaaa gagtcacaga agaggatgaa ggtgtctatc actgcaaagc 2450 caccaaccag aagggctctg tggaaagttc agcatacctc actgttcaag 2500 gaacctcgga caagtctaat ctggagctga tcactctaac atgcacctgt 2550 gtggctgcga ctctcttctg gctcctatta accctcttta tccgaaaaat 2600 gaaaaggtct tcttctgaaa taaagactga ctacctatca attataatgg 2650 acccagatga agttcctttg gatgagcagt gtgagcggct cccttatgat 2700 gccagcaagt gggagtttgc ccgggagaga cttaaactgg gcaaatcact 2750 tggaagaggg gcttttggaa aagtggttca agcatcagca tttggcatta 2800 agaaatcacc tacgtgccgg actgtggctg tgaaaatgct gaaagagggg 2850 gccacggcca gcgagtacaa agctctgatg actgagctaa aaatcttgac 2900 ccacattggc caccatctga acgtggttaa cctgctggga gcctgcacca 2950 agcaaggagg gcctctgatg gtgattgttg aatactgcaa atatggaaat 3000 ctctccaact acctcaagag caaacgtgac ttattttttc tcaacaagga 3050 tgcagcacta cacatggagc ctaagaaaga aaaaatggag ccaggcctgg 3100 aacaaggcaa gaaaccaaga ctagatagcg tcaccagcag cgaaagcttt 3150 gcgagctccg gctttcagga agataaaagt ctgagtgatg ttgaggaaga 3200 ggaggattct gacggtttct acaaggagcc catcactatg gaagatctga 3250 tttcttacag ttttcaagtg gccagaggca tggagttcct gtcttccaga 3300 aagtgcattc atcgggacct ggcagcgaga aacattcttt tatctgagaa 3350 caacgtggtg aagatttgtg attttggcct tgcccgggat atttataaga 3400 accccgatta tgtgagaaaa ggagatactc gacttcctct gaaatggatg 3450 gctcctgaat ctatctttga caaaatctac agcaccaaga gcgacgtgtg 3500 gtcttacgga gtattgctgt gggaaatctt ctccttaggt gggtctccat 3550 acccaggagt acaaatggat gaggactttt gcagtcgcct gagggaaggc 3600 atgaggatga gagctcctga gtactctact cctgaaatct atcagatcat 3650 gctggactgc tggcacagag acccaaaaga aaggccaaga tttgcagaac 3700 ttgtggaaaa actaggtgat ttgcttcaag caaatgtaca acaggatggt 3750 aaagactaca tcccaatcaa tgccatactg acaggaaata gtgggtttac 3800 atactcaact cctgccttct ctgaggactt cttcaaggaa agtatttcag 3850 ctccgaagtt taattcagga agctctgatg atgtcagata cgtaaatgct 3900 ttcaagttca tgagcctgga aagaatcaaa acctttgaag aacttttacc 3950 gaatgccacc tccatgtttg atgactacca gggcgacagc agcactctgt 4000 tggcctctcc catgctgaag cgcttcacct ggactgacag caaacccaag 4050 gcctcgctca agattgactt gagagtaacc agtaaaagta aggagtcggg 4100 gctgtctgat gtcagcaggc ccagtttctg ccattccagc tgtgggcacg 4150 tcagcgaagg caagcgcagg ttcacctacg accacgctga gctggaaagg 4200 aaaatcgcgt gctgctcccc gcccccagac tacaactcgg tggtcctgta 4250 ctccacccca cccatctaga gtttgacacg aagccttatt tctagaagca 4300 catgtgtatt tataccccca ggaaactagc ttttgccagt attatgcata 4350 tataagttta cacctttatc tttccatggg agccagctgc tttttgtgat 4400 ttttttaata gtgctttttt ttttttgact aacaagaatg taactccaga 4450 tagagaaata gtgacaagtg aagaacacta ctgctaaatc ctcatgttac 4500 tcagtgttag agaaatcctt cctaaaccca atgacttccc tgctccaacc 4550 cccgccacct cagggcacgc aggaccagtt tgattgagga gctgcactga 4600 tcacccaatg catcacgtac cccactgggc cagccctgca gcccaaaacc 4650 cagggcaaca agcccgttag ccccagggat cactggctgg cctgagcaac 4700 atctcgggag tcctctagca ggcctaagac atgtgaggag gaaaaggaaa 4750 aaaagcaaaa agcaagggag aaaagagaaa ccgggagaag gcatgagaaa 4800 gaatttgaga cgcaccatgt gggcacggag ggggacgggg ctcagcaatg 4850 ccatttcagt ggcttcccag ctctgaccct tctacatttg agggcccagc 4900 caggagcaga tggacagcga tgaggggaca ttttctggat tctgggaggc 4950 aagaaaagga caaatatctt ttttggaact aaagcaaatt ttagaacttt 5000 acctatggaa gtggttctat gtccattctc attcgtggca tgttttgatt 5050 tgtagcactg agggtggcac tcaactctga gcccatactt ttggctcctc 5100 tagtaagatg cactgaaaac ttagccagag ttaggttgtc tccaggccat 5150 gatggcctta cactgaaaat gtcacattct attttgggta ttaatatata 5200 gtccagacac ttaactcaat ttcttggtat tattctgttt tgcacagtta 5250 gttgtgaaag aaagctgaga agaatgaaaa tgcagtcctg aggagaggag 5300 ttttctccat atcaaaacga gggctgatgg aggaaaaagg tcaataaggt 5350 caagggaaaa ccccgtctct ataccaacca aaccaattca ccaacacagt 5400 tgggacccaa aacacaggaa gtcagtcacg tttccttttc atttaatggg 5450 gattccacta tctcacacta atctgaaagg atgtggaaga gcattagctg 5500 gcgcatatta agcactttaa gctccttgag taaaaaggtg gtatgtaatt 5550 tatgcaaggt atttctccag ttgggactca ggatattagt taatgagcca 5600 tcactagaag aaaagcccat tttcaactgc tttgaaactt gcctggggtc 5650 tgagcatgat gggaataggg agacagggta ggaaagggcg cctactcttc 5700 agggtctaaa gatcaagtgg gccttggatc gctaagctgg ctctgtttga 5750 tgctatttat gcaagttagg gtctatgtat tta 5783 ccatcattca aatctgttaa cacctcagtg catatatatg ataaagcatt 1250 catcactgtg aaacatcgaa aacagcaggt gcttgaaacc gtagctggca 1300 agcggtctta ccggctctct atgaaagtga aggcatttcc ctcgccggaa 1350 gttgtatggt taaaagatgg gttacctgcg actgagaaat ctgctcgcta 1400 tttgactcgt ggctactcgt taattatcaa ggacgtaact gaagaggatg 1450 tacaatcttg cagggaatta ctgagcataa aacagtcaaa tgtgtttaaa 1500 aacctcactg ccactctaat tgtcaatgtg tttacgaaaa aaaccccaga 1550 ggccgtgtca tcgtttccag acccggctct ctacccactg ggcagcagac 1600 ttgtaccgca aaatcctgac tatggtatcc ctcaacctac aatcaagtgg 1650 ttctggcacc cctgtaacca taatcattcc gaagcaaggt gtgacttttg 1700 ttccaataat gaagagtcct ttatcctgga tgctgacagc aacatgggaa 1750 acagaattga gagcatcact cagcgcatgg caataataga aggaaagaat 1800 aagatggcta gcaccttggt tgtggctgac tctagaattt ctggaatcta 1850 gcttccaata catttgcata tgtgggaaga aagttgggac aacataagct 1900 tttatatcac agatgtgcca aatgggtttc atgttaactt ggaaaaaatg 1950 ccgacggaag gagaggacct gaaactgtct tgcacagtta acaagttctt 2000 atacagagac gttacttgga ttt tactgcg gacagttaat aacagaacaa 2050 tgcactacag tattagcaag caaaaaatgg ccatcactaa ggagcactcc 2100 atcactctta atcttaccat catgaatgtt tccctgcaag attcaggcac 2150 ctatgcctgc agagccagga atgtatacac aggggaagaa atcctccaga 2200 agaaagaaat tacaatcaga gatcaggaag caccatacct cctgcgaaac 2250 ctcagtgatc acacagtggc catcagcagt tccaccactt tagactgtca 2300 tgctaatggt gtccccgagc ctcagatcac aacaaccaca ttggtttaaa 2350 agagcctgga aaatacaaca attattttag gaccaggaag cagcacgctg 2400 gagtcacaga tttattgaaa agaggatgaa ggtgtctatc actgcaaagc 2450 caccaaccag aagggctctg tggaaagttc agcatacctc actgttcaag 2500 gaacctcgga caagtctaat ctggagctga tcactctaac atgcacctgt 2550 gtggctgcga ctctcttctg gctcctatta accctcttta tccgaaaaat 2600 tcttctgaaa gaaaaggtct taaagactga ctacctatca attataatgg 2650 acccagatga agttcctttg gatgagcagt gtgagcggct cccttatgat 2700 gccagcaagt gggagtttgc ccgggagaga cttaaactgg gcaaatcact 2750 gcttttggaa tggaagaggg aagtggttca agcatcagca tttggcatta 2800 agaaatcacc tacgtgccgg actgtggctg tgaaaatgct gaaag AGGGG 2850 gcgagtacaa gccacggcca agctctgatg actgagctaa aaatcttgac 2900 caccatctga ccacattggc acgtggttaa cctgctggga gcctgcacca 2950 agcaaggagg gcctctgatg gtgattgttg aatactgcaa atatggaaat 3000 ctctccaact acctcaagag caaacgtgac ttattttttc tcaacaagga 3050 cacatggagc tgcagcacta ctaagaaaga aaaaatggag ccaggcctgg 3100 gaaaccaaga aacaaggcaa ctagatagcg tcaccagcag cgaaagcttt 3150 gcgagctccg gctttcagga agataaaagt ctgagtgatg ttgaggaaga 3200 ggaggattct gacggtttct acaaggagcc catcactatg gaagatctga 3250 tttcttacag ttttcaagtg gccagaggca tggagttcct gtcttccaga 3300 aagtgcattc atcgggacct ggcagcgaga aacattcttt tatctgagaa 3350 caacgtggtg aagatttgtg attttggcct tgcccgggat atttataaga 3400 accccgatta tgtgagaaaa ggagatactc gacttcctct gaaatggatg 3450 gctcctgaat ctatctttga caaaatctac agcaccaaga gcgacgtgtg 3500 gtcttacgga gtattgctgt gggaaatctt ctccttaggt gggtctccat 3550 acccaggagt acaaatggat gaggactttt gcagtcgcct gagggaaggc 3600 gagctcctga atgaggatga gtactctact cctgaaatct atcagatcat 3650 gctggactgc t ggcacagag acccaaaaga aaggccaaga tttgcagaac 3700 ttgtggaaaa actaggtgat ttgcttcaag caaatgtaca acaggatggt 3750 tcccaatcaa aaagactaca tgccatactg acaggaaata gtgggtttac 3800 atactcaact cctgccttct ctgaggactt cttcaaggaa agtatttcag 3850 ctccgaagtt taattcagga agctctgatg atgtcagata cgtaaatgct 3900 tgagcctgga ttcaagttca aagaatcaaa acctttgaag aacttttacc 3950 gaatgccacc tccatgtttg atgactacca gggcgacagc agcactctgt 4000 tggcctctcc catgctgaag cgcttcacct ggactgacag caaacccaag 4050 gcctcgctca agattgactt gagagtaacc agtaaaagta aggagtcggg 4100 gctgtctgat gtcagcaggc ccagtttctg ccattccagc tgtgggcacg 4150 tcagcgaagg caagcgcagg ttcacctacg accacgctga gctggaaagg 4200 aaaatcgcgt gctgctcccc gcccccagac tacaactcgg tggtcctgta 4250 cccatctaga ctccacccca gtttgacacg aagccttatt tctagaagca 4300 catgtgtatt tataccccca ggaaactagc ttttgccagt attatgcata 4350 tataagttta cacctttatc tttccatggg agccagctgc tttttgtgat 4400 ttttttaata gtgctttttt ttttttgact aacaagaatg taactccaga 4450 tagagaaata gtgacaagtg ctg aagaacacta ctaaatc ctcatgttac 4500 tcagtgttag agaaatcctt cctaaaccca atgacttccc tgctccaacc 4550 cccgccacct cagggcacgc aggaccagtt tgattgagga gctgcactga 4600 tcacccaatg catcacgtac cccactgggc cagccctgca gcccaaaacc 4650 cagggcaaca agcccgttag ccccagggat cactggctgg cctgagcaac 4700 atctcgggag tcctctagca ggcctaagac atgtgaggag gaaaaggaaa 4750 aaaagcaaaa agcaagggag aaaagagaaa ccgggagaag gcatgagaaa 4800 gaatttgaga cgcaccatgt gggcacggag ggggacgggg ctcagcaatg 4850 ccatttcagt ggcttcccag ctctgaccct tctacatttg agggcccagc 4900 tggacagcga caggagcaga tgaggggaca ttttctggat tctgggaggc aagaaaagga 4950 caaatatctt ttttggaact aaagcaaatt ttagaacttt 5000 acctatggaa gtggttctat gtccattctc attcgtggca tgttttgatt 5050 tgtagcactg agggtggcac tcaactctga gcccatactt ttggctcctc 5100 tagtaagatg cactgaaaac ttagccagag ttaggttgtc tccaggccat 5150 gatggcctta cactgaaaat attttgggta gtcacattct ttaatatata 5200 gtccagacac ttaactcaat ttcttggtat tattctgttt tgcacagtta 5250 gttgtgaaag aaagctgaga agaatgaaaa tgcagtcctg aggagaggag 5300 ttttctccat atcaaaacga gggctgatgg aggaaaaagg tcaataaggt 5350 ccccgtctct caagggaaaa aaccaattca ataccaacca ccaacacagt 5400 aacacaggaa tgggacccaa gtcagtcacg tttccttttc atttaatggg 5450 tctcacacta gattccacta atctgaaagg atgtggaaga gcattagctg 5500 agcactttaa gcgcatatta gctccttgag taaaaaggtg gtatgtaatt 5550 tatgcaaggt atttctccag ttgggactca ggatattagt taatgagcca 5600 tcactagaag aaaagcccat tttcaactgc tttgaaactt gcctggggtc 5650 tgagcatgat gggaataggg agacagggta ggaaagggcg cctactcttc 5700 agggtctaaa gatcaagtgg gccttggatc gctaagctgg ctctgtttga 5750 tgctatttat gcaagttagg gtctatgtat tta 5783

<210> 7 <210> 7

<211> 3496 <211> 3496

<212> ADN <212> DNA

<213> Homo sapiens <213> Homo sapiens

<400> 7<400> 7

acctgcagcg cgaggcgcgc cgctccaggc ggcatcgcag ggctgggccg 50 gcgcggcctg gggaccccgg gctccggagg ccatgccggc gttggcgcgc 100 gacggcggcc agctgccgct gctcgttgtt ttttctgcaa tgatatttgg 150 gactattaca aatcaagatc tgcctgtgat caagtgtgtt ttaatcaatc 200 ataagaacaa tgattcatca gtggggaagt catcatcata tcccatggta 250 tcagaatccc cggaagacct cgggtgtgcg ttgagacccc agagctcagg 300 gacagtgtac gaagctgccg ctgtggaagt ggatgtatct gcttccatca 350 cactgcaagt gctggtcgac gccccaggga acatttcctg tctctgggtc 400 tttaagcaca gctccctgaa ttgccagcca cattttgatt tacaaaacag 450 aggagttgtt tccatggtca ttttgaaaat gacagaaacc caagctggag 500 aatacctact ttttattcag agtgaagcta ccaattacac aatattgttt 550 acagtgagta taagaaatac cctgctttac acattaagaa gaccttactt 600 tagaaaaatg gaaaaccagg acgccctggt ctgcatatct gagagcgttc 650 cagagccgat cgtggaatgg gtgctttgcg attcacaggg ggaaagctgt 700 aaagaagaaa gtccagctgt tgttaaaaag gaggaaaaag tgcttcatga 750 attatttggg acggacataa ggtgctgtgc cagaaatgaa ctgggcaggg 800 aatgcaccag gctgttcaca atagatctaa atcaaactcc tcagaccaca 850 ttgccacaat tatttcttaa agtaggggaa cccttatgga taaggtgcaa 900 agctgttcat gtgaaccatg gattcgggct cacctgggaa ttagaaaaca 950 aagcactcga ggagggcaac tactttgaga tgagtaccta ttcaacaaac 1000 agaactatga tacggattct gtttgctttt gtatcatcag tggcaagaaa 1050 cgacaccgga tactacactt gttcctcttc aaagcatccc agtcaatcag 1100 ctttggttac catcgtagaa aagggattta taaatgctac caattcaagt 1150 gaagattatg aaattgacca atatgaagag ttttgttttt ctgtcaggtt 1200 taaagcctac ccacaaatca gatgtacgtg gaccttctct cgaaaatcat 1250 ttccttgtga gcaaaagggt cttgataacg gatacagcat atccaagttt 1300 tgcaatcata agcaccagcc aggagaatat atattccatg cagaaaatga 1350 tgatgcccaa tttaccaaaa tgttcacgct gaatataaga aggaaacctc 1400 aagtgctcgc agaagcatcg gcaagtcagg cgtcctgttt ctcggatgga 1450 tacccattac catcttggac ctggaagaag tgttcagaca agtctcccaa 1500 ctgcacagaa gagatcacag aaggagtctg gaatagaaag gctaacagaa 1550 aagtgtttgg acagtgggtg tcgagcagta ctctaaacat gagtgaagcc 1600 ataaaagggt tcctggtcaa gtgctgtgca tacaattccc ttggcacatc 1650 ttgtgagacg atccttttaa actctccagg ccccttccct ttcatccaag 1700 acaacatctc attctatgca acaattggtg tttgtctcct cttcattgtc 1750 gttttaaccc tgctaatttg tcacaagtac aaaaagcaat ttaggtatga 1800 aagccagcta cagatggtac aggtgaccgg ctcctcagat aatgagtact 1850 tctacgttga tttcagagaa tatgaatatg atctcaaatg ggagtttcca 1900 agagaaaatt tagagtttgg gaaggtacta ggatcaggtg cttttggaaa 1950 agtgatgaac gcaacagctt atggaattag caaaacagga gtctcaatcc 2000 aggttgccgt caaaatgctg aaagaaaaag cagacagctc tgaaagagag 2050 gcactcatgt cagaactcaa gatgatgacc cagctgggaa gccacgagaa 2100 tattgtgaac ctgctggggg cgtgcacact gtcaggacca atttacttga 2150 tttttgaata ctgttgctat ggtgatcttc tcaactatct aagaagtaaa 2200 agagaaaaat ttcacaggac ttggacagag attttcaagg aacacaattt 2250 cagtttttac cccactttcc aatcacatcc aaattccagc atgcctggtt 2300 caagagaagt tcagatacac ccggactcgg atcaaatctc agggcttcat 2350 gggaattcat ttcactctga agatgaaatt gaatatgaaa accaaaaaag 2400 gctggaagaa gaggaggact tgaatgtgct tacatttgaa gatcttcttt 2450 gctttgcata tcaagttgcc aaaggaatgg aatttctgga atttaagtcg 2500 tgtgttcaca gagacctggc cgccaggaac gtgcttgtca cccacgggaa 2550 agtggtgaag atatgtgact ttggattggc tcgagatatc atgagtgatt 2600 ccaactatgt tgtcaggggc aatgcccgtc tgcctgtaaa atggatggcc 2650 cccgaaagcc tgtttgaagg catctacacc attaagagtg atgtctggtc 2700 atatggaata ttactgtggg aaatcttctc acttggtgtg aatccttacc 2750 ctggcattcc ggttgatgct aacttctaca aactgattca aaatggattt 2800 aaaatggatc agccatttta tgctacagaa gaaatataca ttataatgca 2850 atcctgctgg gcttttgact caaggaaacg gccatccttc cctaatttga 2900 cttcgttttt aggatgtcag ctggcagatg cagaagaagc gatgtatcag 2950 aatgtggatg gccgtgtttc ggaatgtcct cacacctacc aaaacaggcg 3000 acctttcagc agagagatgg atttggggct actctctccg caggctcagg 3050 tcgaagattc gtagaggaac aatttagttt taaggacttc atccctccac 3100 ctatccctaa caggctgtag attaccaaaa caagattaat ttcatcacta 3150 aaagaaaatc tattatcaac tgctgcttca ccagactttt ctctagaagc 3200 tgtctgcgtt tactcttgtt ttcaaaggga cttttgtaaa atcaaatcat 3250 cctgtcacaa ggcaggagga gctgataatg aactttattg gagcattgat 3300 ctgcatccaa ggccttctca ggctggcttg agtgaattgt gtacctgaag 3350 tacagtatat tcttgtaaat acataaaaca aaagcatttt gctaaggaga 3400 agctaatatg attttttaag tctatgtttt aaaataatat gtaaattttt 3450 cagctattta gtgatatatt ttatgggtgg gaataaaatt tctact 3496 acctgcagcg cgaggcgcgc cgctccaggc ggcatcgcag ggctgggccg 50 gcgcggcctg gggaccccgg gctccggagg ccatgccggc gttggcgcgc 100 gacggcggcc agctgccgct gctcgttgtt ttttctgcaa tgatatttgg 150 gactattaca aatcaagatc tgcctgtgat caagtgtgtt ttaatcaatc 200 tgattcatca ataagaacaa gtggggaagt catcatcata tcccatggta 250 tcagaatccc cggaagacct cgggtgtgcg ttgagacccc agagctcagg 300 gacagtgtac gaagctgccg ctgtggaagt ggatgtatct gcttccatca 350 cactgcaagt gctggtcgac gccccaggga acatttcctg tctctgggtc 400 gctccctgaa tttaagcaca ttgccagcca cattttgatt tacaaaacag 450 aggagttgtt tccatggtca ttttgaaaat gacagaaacc caagctggag 500 aatacctact ttttattcag agtgaagcta ccaattacac aatattgttt 550 acagtgagta taagaaatac cctgctttac acattaagaa gaccttactt 600 tagaaaaatg gaaaaccagg acgccctggt ctgcatatct gagagcgttc 650 cagagccgat cgtggaatgg gtgctttgcg attcacaggg ggaaagctgt 700 aaagaagaaa gtccagctgt tgttaaaaag gaggaaaaag tgcttcatga 750 attatttggg acggacataa ggtgctgtgc cagaaatgaa ctgggcaggg 800 gctgttcaca aatgcaccag atagatctaa atcaaactc tcagaccaca c 850 ttgccacaat tatttcttaa agtaggggaa taaggtgcaa cccttatgga 900 agctgttcat gtgaaccatg gattcgggct ttagaaaaca cacctgggaa 950 ggagggcaac aagcactcga tactttgaga tgagtaccta ttcaacaaac 1000 agaactatga tacggattct gtttgctttt gtatcatcag tggcaagaaa 1050 cgacaccgga tactacactt gttcctcttc aaagcatccc agtcaatcag 1100 ctttggttac catcgtagaa aagggattta taaatgctac caattcaagt 1150 aaattgacca gaagattatg atatgaagag ttttgttttt ctgtcaggtt 1200 taaagcctac ccacaaatca gatgtacgtg gaccttctct cgaaaatcat 1250 ttccttgtga gcaaaagggt cttgataacg gatacagcat atccaagttt 1300 tgcaatcata agcaccagcc aggagaatat atattccatg cagaaaatga 1350 tttaccaaaa tgatgcccaa tgttcacgct gaatataaga aggaaacctc 1400 aagtgctcgc agaagcatcg gcaagtcagg cgtcctgttt ctcggatgga 1450 tacccattac catcttggac ctggaagaag tgttcagaca agtctcccaa 1500 ctgcacagaa gagatcacag aaggagtctg gaatagaaag gctaacagaa 1550 aagtgtttgg acagtgggtg tcgagcagta ctctaaacat gagtgaagcc 1600 tcctggtcaa ataaaagggt gtgctgtgca tacaattccc ttggcacatc 1650 ttgtgaga cg atccttttaa actctccagg ccccttccct ttcatccaag 1700 attctatgca acaacatctc acaattggtg tttgtctcct cttcattgtc 1750 gttttaaccc tgctaatttg tcacaagtac aaaaagcaat ttaggtatga 1800 aagccagcta cagatggtac aggtgaccgg ctcctcagat aatgagtact 1850 tttcagagaa tctacgttga tatgaatatg atctcaaatg ggagtttcca 1900 agagaaaatt tagagtttgg gaaggtacta ggatcaggtg cttttggaaa 1950 agtgatgaac gcaacagctt atggaattag caaaacagga gtctcaatcc 2000 aggttgccgt caaaatgctg aaagaaaaag cagacagctc tgaaagagag 2050 cagaactcaa gcactcatgt gatgatgacc gccacgagaa cagctgggaa 2100 tattgtgaac ctgctggggg cgtgcacact gtcaggacca atttacttga 2150 tttttgaata ctgttgctat ggtgatcttc tcaactatct aagaagtaaa 2200 agagaaaaat ttcacaggac ttggacagag attttcaagg aacacaattt 2250 cagtttttac cccactttcc aatcacatcc aaattccagc atgcctggtt 2300 caagagaagt tcagatacac ccggactcgg atcaaatctc agggcttcat 2350 gggaattcat ttcactctga agatgaaatt gaatatgaaa accaaaaaag 2400 gctggaagaa gaggaggact tgaatgtgct tacatttgaa gatcttcttt 2450 gctttgcata tcaagttgcc aaaggaatgg aatttctgga atttaagtcg 2500 gagacctggc tgtgttcaca cgccaggaac gtgcttgtca cccacgggaa 2550 agtggtgaag atatgtgact ttggattggc tcgagatatc atgagtgatt 2600 ccaactatgt tgtcaggggc aatgcccgtc tgcctgtaaa atggatggcc 2650 cccgaaagcc tgtttgaagg catctacacc attaagagtg atgtctggtc 2700 atatggaata ttactgtggg aaatcttctc acttggtgtg aatccttacc 2750 ggttgatgct ctggcattcc aacttctaca aactgattca aaatggattt 2800 agccatttta aaaatggatc tgctacagaa gaaatataca ttataatgca 2850 atcctgctgg gcttttgact caaggaaacg gccatccttc cctaatttga 2900 cttcgttttt aggatgtcag ctggcagatg cagaagaagc gatgtatcag 2950 aatgtggatg gccgtgtttc ggaatgtcct cacacctacc aaaacaggcg 3000 acctttcagc agagagatgg atttggggct actctctccg caggctcagg 3050 tcgaagattc gtagaggaac aatttagttt taaggacttc atccctccac 3100 ctatccctaa caggctgtag attaccaaaa caagattaat ttcatcacta 3150 aaagaaaatc tattatcaac tgctgcttca ccagactttt ctctagaagc 3200 tgtctgcgtt tactcttgtt ttcaaaggga cttttgtaaa atcaaatcat 3250 ggcaggagga cctgtcacaa gctgataatg aactttattg gagcattgat 3 300 ctgcatccaa ggccttctca ggctggcttg agtgaattgt gtacctgaag 3350 tacagtatat tcttgtaaat acataaaaca aaagcatttt gctaaggaga 3400 agctaatatg attttttaag tctatgtttt aaaataatat gtaaatttta 3450

<210> 8 <210> 8

<211> 8707 <211> 8707

<212> ADN <212> DNA

<213> Homo sapiens <213> Homo sapiens

<400> 8<400> 8

gcggggaagg cgggcggtgg ggcagggggc ctgaagcggc ggtaccggtg 50 ctggcggcgg cagctgaggc cttggccgaa gccgcgcgaa cctcagggca 100 agatgcttgg aaccggacct gccgccgcca ccaccgctgc caccacatct 150 agcaatgtga gcgtcctgca gcagtttgcc agtggcctaa agagccggaa 200 tgaggaaacc agggccaaag ccgccaagga gctccagcac tatgtcacca 250 tggaactccg agagatgagt caagaggagt ctactcgctt ctatgaccaa 300 ctgaaccatc acatttttga attggtttcc agctcagatg ccaatgagag 350 gaaaggtggc atcttggcca tagctagcct cataggagtg gaaggtggga 400 atgccacccg aattggcaga tttgccaact atcttcggaa cctcctcccc 450 tccaatgacc cagttgtcat ggaaatggca tccaaggcca ttggccgtct 500 tgccatggca ggggacactt ttaccgctga gtacgtggaa tttgaggtga 550 agcgagccct ggaatggctg ggtgctgacc gcaatgaggg ccggagacat 600 gcagctgtcc tggttctccg tgagctggcc atcagcgtcc ctaccttctt 650 cttccagcaa gtgcaaccct tctttgacaa catttttgtg gccgtgtggg 700 accccaaaca ggccatccgt gagggagctg tagccgccct tcgtgcctgt 750 ctgattctca caacccagcg tgagccgaag gagatgcaga agcctcagtg 800 gtacaggcac acatttgaag aagcagagaa gggatttgat gagaccttgg 850 ccaaagagaa gggcatgaat cgggatgatc ggatccatgg agccttgttg 900 atccttaacg agctggtccg aatcagcagc atggagggag agcgtctgag 950 agaagaaatg gaagaaatca cacagcagca gctggtacac gacaagtact 1000 gcaaagatct catgggcttc ggaacaaaac ctcgtcacat tacccccttc 1050 accagtttcc aggctgtaca gccccagcag tcaaatgcct tggtggggct 1100 gctggggtac agctctcacc aaggcctcat gggatttggg acctccccca 1150 gtccagctaa gtccaccctg gtggagagcc ggtgttgcag agacttgatg 1200 gaggagaaat ttgatcaggt gtgccagtgg gtgctgaaat gcaggaatag 1250 caagaactcg ctgatccaaa tgacaatcct taatttgttg ccccgcttgg 1300 ctgcattccg accttctgcc ttcacagata cccagtatct ccaagatacc 1350 atgaaccatg tcctaagctg tgtcaagaag gagaaggaac gtacagcggc 1400 cttccaagcc ctggggctac tttctgtggc tgtgaggtct gagtttaagg 1450 tctatttgcc tcgcgtgctg gacatcatcc gagcggccct gcccccaaag 1500 gacttcgccc ataagaggca gaaggcaatg caggtggatg ccacagtctt 1550 cacttgcatc agcatgctgg ctcgagcaat ggggccaggc atccagcagg 1600 atatcaagga gctgctggag cccatgctgg cagtgggact aagccctgcc 1650 ctcactgcag tgctctacga cctgagccgt cagattccac agctaaagaa 1700 ggacattcaa gatgggctac tgaaaatgct gtccctggtc cttatgcaca 1750 aaccccttcg ccacccaggc atgcccaagg gcctggccca tcagctggcc 1800 tctcctggcc tcacgaccct ccctgaggcc agcgatgtgg gcagcatcac 1850 tcttgccctc cgaacgcttg gcagctttga atttgaaggc cactctctga 1900 cccaatttgt tcgccactgt gcggatcatt tcctgaacag tgagcacaag 1950 gagatccgca tggaggctgc ccgcacctgc tcccgcctgc tcacaccctc 2000 catccacctc atcagtggcc atgctcatgt ggttagccag accgcagtgc 2050 aagtggtggc agatgtgctt agcaaactgc tcgtagttgg gataacagat 2100 cctgaccctg acattcgcta ctgtgtcttg gcgtccctgg acgagcgctt 2150 tgatgcacac ctggcccagg cggagaactt gcaggccttg tttgtggctc 2200 tgaatgacca ggtgtttgag atccgggagc tggccatctg cactgtgggc 2250 cgactcagta gcatgaaccc tgcctttgtc atgcctttcc tgcgcaagat 2300 gctcatccag attttgacag agttggagca cagtgggatt ggaagaatca 2350 aagagcagag tgcccgcatg ctggggcacc tggtctccaa tgccccccga 2400 ctcatccgcc cctacatgga gcctattctg aaggcattaa ttttgaaact 2450 gaaagatcca gaccctgatc caaacccagg tgtgatcaat aatgtcctgg 2500 caacaatagg agaattggca caggttagtg gcctggaaat gaggaaatgg 2550 gttgatgaac tttttattat catcatggac atgctccagg attcctcttt 2600 gttggccaaa aggcaggtgg ctctgtggac cctgggacag ttggtggcca 2650 gcactggcta tgtagtagag ccctacagga agtaccctac tttgcttgag 2700 gtgctactga attttctgaa gactgagcag aaccagggta cacgcagaga 2750 ggccatccgt gtgttagggc ttttaggggc tttggatcct tacaagcaca 2800 aagtgaacat tggcatgata gaccagtccc gggatgcctc tgctgtcagc 2850 ctgtcagaat ccaagtcaag tcaggattcc tctgactata gcactagtga 2900 aatgctggtc aacatgggaa acttgcctct ggatgagttc tacccagctg 2950 tgtccatggt ggccctgatg cggatcttcc gagaccagtc actctctcat 3000 catcacacca tggttgtcca ggccatcacc ttcatcttca agtccctggg 3050 actcaaatgt gtgcagttcc tgccccaggt catgcccacg ttccttaacg 3100 tcattcgagt ctgtgatggg gccatccggg aatttttgtt ccagcagctg 3150 ggaatgttgg tgtcctttgt gaagagccac atcagacctt atatggatga 3200 aatagtcacc ctcatgagag aattctgggt catgaacacc tcaattcaga 3250 gcacgatcat tcttctcatt gagcaaattg tggtagctct tgggggtgaa 3300 tttaagctct acctgcccca gctgatccca cacatgctgc gtgtcttcat 3350 gcatgacaac agcccaggcc gcattgtctc tatcaagtta ctggctgcaa 3400 tccagctgtt tggcgccaac ctggatgact acctgcattt actgctgcct 3450 cctattgtta agttgtttga tgcccctgaa gctccactgc catctcgaaa 3500 ggcagcgcta gagactgtgg accgcctgac ggagtccctg gatttcactg 3550 actatgcctc ccggatcatt caccctattg ttcgaacact ggaccagagc 3600 ccagaactgc gctccacagc catggacacg ctgtcttcac ttgtttttca 3650 gctggggaag aagtaccaaa ttttcattcc aatggtgaat aaagttctgg 3700 tgcgacaccg aatcaatcat cagcgctatg atgtgctcat ctgcagaatt 3750 gtcaagggat acacacttgc tgatgaagag gaggatcctt tgatttacca 3800 gcatcggatg cttaggagtg gccaagggga tgcattggct agtggaccag 3850 tggaaacagg acccatgaag aaactgcacg tcagcaccat caacctccaa 3900 aaggcaaccg cctggggcgc tgccaggagg gtctccaaag atgactggct 3950 ggaatggctg agacggctga gcctggagct gctgaaggac tcatcatcgc 4000 cctccctgcg ctcctgctgg gccctggcac aggcctacaa cccgatggcc 4050 agggatctct tcaatgctgc atttgtgtcc tgctggtctg aactgaatga 4100 agatcaacag gatgagctca tcagaagcat cgagttggcc ctcacctcac 4150 aagacatcgc tgaagtcaca cagaccctct taaacttggc tgaattcatg 4200 gaacacagtg acaagggccc cctgccactg agagatgaca atggcattgt 4250 tctgctgggt gagagagctg ccaagtgccg agcatatgcc aaagcactac 4300 actacaaaga actggagttc cagaaaggcc ccacccctgc cattctagaa 4350 tctctcatca gcattaataa taagctacag cagccggagg cagcggccgg 4400 agtgttagaa tatgccatga aacactttgg agagctggag atccaggcta 4450 cctggtatga gaaactgcac gagtgggagg atgcccttgt ggcctatgac 4500 aagaaaatgg acaccaacaa ggacgaccca gagctgatgc tgggccgcat 4550 gcgctgcctc gaggccttgg gggaatgggg tcaactccac cagcagtgct 4600 gtgaaaagtg gaccctggtt aatgatgaga cccaagccaa gatggcccgg 4650 atggctgctg cagctgcatg gggtttaggt cagtgggaca gcatggaaga 4700 atacacctgt atgatccctc gggacaccca tgatggggca ttttatagag 4750 ctgtgctggc actgcatcag gacctcttct ccttggcaca acagtgcatt 4800 gacaaggcca gggacctgct ggatgctgaa ttaactgcga tggcaggaga 4850 gagttacagt cgggcatatg gggccatggt ttcttgccac atgctgtccg 4900 agctggagga ggttatccag tacaaacttg tccccgagcg acgagagatc 4950 atccgccaga tctggtggga gagactgcag ggctgccagc gtatcgtaga 5000 ggactggcag aaaatcctta tggtgcggtc ccttgtggtc agccctcatg 5050 aagacatgag aacctggctc aagtatgcaa gcctgtgcgg caagagtggc 5100 aggctggctc ttgctcataa aactttagtg ttgctcctgg gagttgatcc 5150 gtctcggcaa cttgaccatc ctctgccaac agttcaccct caggtgacct 5200 atgcctacat gaaaaacatg tggaagagtg cccgcaagat cgatgccttc 5250 cagcacatgc agcattttgt ccagaccatg cagcaacagg cccagcatgc 5300 catcgctact gaggaccagc agcataagca ggaactgcac aagctcatgg 5350 cccgatgctt cctgaaactt ggagagtggc agctgaatct acagggcatc 5400 aatgagagca caatccccaa agtgctgcag tactacagcg ccgccacaga 5450 gcacgaccgc agctggtaca aggcctggca tgcgtgggca gtgatgaact 5500 tcgaagctgt gctacactac aaacatcaga accaagcccg cgatgagaag 5550 aagaaactgc gtcatgccag cggggccaac atcaccaacg ccaccactgc 5600 cgccaccacg gccgccactg ccaccaccac tgccagcacc gagggcagca 5650 acagtgagag cgaggccgag agcaccgaga acagccccac cccatcgccg 5700 ctgcagaaga aggtcactga ggatctgtcc aaaaccctcc tgatgtacac 5750 ggtgcctgcc gtccagggct tcttccgttc catctccttg tcacgaggca 5800 acaacctcca ggatacactc agagttctca ccttatggtt tgattatggt 5850 cactggccag atgtcaatga ggccttagtg gagggggtga aagccatcca 5900 gattgatacc tggctacagg ttatacctca gctcattgca agaattgata 5950 cgcccagacc cttggtggga cgtctcattc accagcttct cacagacatt 6000 ggtcggtacc acccccaggc cctcatctac ccactgacag tggcttctaa 6050 gtctaccacg acagcccggc acaatgcagc caacaagatt ctgaagaaca 6100 tgtgtgagca cagcaacacc ctggtccagc aggccatgat ggtgagcgag 6150 gagctgatcc gagtggccat cctctggcat gagatgtggc atgaaggcct 6200 ggaagaggca tctcgtttgt actttgggga aaggaacgtg aaaggcatgt 6250 ttgaggtgct ggagcccttg catgctatga tggaacgggg cccccagact 6300 ctgaaggaaa catcctttaa tcaggcctat ggtcgagatt taatggaggc 6350 ccaagagtgg tgcaggaagt acatgaaatc agggaatgtc aaggacctca 6400 cccaagcctg ggacctctat tatcatgtgt tccgacgaat ctcaaagcag 6450 ctgcctcagc tcacatcctt agagctgcaa tatgtttccc caaaacttct 6500 gatgtgccgg gaccttgaat tggctgtgcc aggaacatat gaccccaacc 6550 agccaatcat tcgcattcag tccatagcac cgtctttgca agtcatcaca 6600 tccaagcaga ggccccggaa attgacactt atgggcagca acggacatga 6650 gtttgttttc cttctaaaag gccatgaaga tctgcgccag gatgagcgtg 6700 tgatgcagct cttcggcctg gttaacaccc ttctggccaa tgacccaaca 6750 tctcttcgga aaaacctcag catccagaga tacgctgtca tccctttatc 6800 gaccaactcg ggcctcattg gctgggttcc ccactgtgac acactgcacg 6850 ccctcatccg ggactacagg gagaagaaga agatccttct caacatcgag 6900 catcgcatca tgttgcggat ggctccggac tatgaccact tgactctgat 6950 gcagaaggtg gaggtgtttg agcatgccgt caataataca gctggggacg 7000 acctggccaa gctgctgtgg ctgaaaagcc ccagctccga ggtgtggttt 7050 gaccgaagaa ccaattatac ccgttcttta gcggtcatgt caatggttgg 7100 gtatatttta ggcctgggag atagacaccc atccaacctg atgctggacc 7150 gtctgagtgg gaagatcctg cacattgact ttggggactg ctttgaggtt 7200 gctatgaccc gagagaagtt tccagagaag attccattta gactaacaag 7250 aatgttgacc aatgctatgg aggttacagg cctggatggc aactacagaa 7300 tcacatgcca cacagtgatg gaggtgctgc gagagcacaa ggacagtgtc 7350 atggccgtgc tggaagcctt tgtctatgac cccttgctga actggaggct 7400 gatggacaca aataccaaag gcaacaagcg atcccgaacg aggacggatt 7450 cctactctgc tggccagtca gtcgaaattt tggacggtgt ggaacttgga 7500 gagccagccc ataagaaaac ggggaccaca gtgccagaat ctattcattc 7550 tttcattgga gacggtttgg tgaaaccaga ggccctaaat aagaaagcta 7600 tccagattat taacagggtt cgagataagc tcactggtcg ggacttctct 7650 catgatgaca ctttggatgt tccaacgcaa gttgagctgc tcatcaaaca 7700 agcgacatcc catgaaaacc tctgccagtg ctatattggc tggtgccctt 7750 tctggtaact ggaggcccag atgtgcccat cacgtttttt ctgaggcttt 7800 tgtactttag taaatgcttc cactaaactg aaaccatggt gagaaagttt 7850 gactttgtta aatattttga aatgtaaatg aaaagaacta ctgtatatta 7900 aaagttggtt tgaaccaact ttctagctgc tgttgaagaa tatattgtca 7950 gaaacacaag gcttgatttg gttcccagga cagtgaaaca tagtaatacc 8000 acgtaaatca agccattcat tttggggaac agaagatcca taactttaga 8050 aatacgggtt ttgacttaac tcacaagaga actcatcata agtacttgct 8100 gatggaagaa tgacctagtt gctcctctca acatgggtac agcaaactca 8150 gcacagccaa gaagcctcag gtcgtggaga acatggatta ggatcctaga 8200 ctgtaaagac acagaagatg ctgacctcac ccctgccacc tatcccaaga 8250 cctcactggt ctgtggacag cagcagaaat gtttgcaaga taggccaaaa 8300 tgagtacaaa aggtctgtct tccatcagac ccagtgatgc tgcgactcac 8350 acgcttcaat tcaagacctg accgctagta gggaggttta ttcagatcgc 8400 tggcagcctc ggctgagcag atgcacagag gggatcactg tgcagtggga 8450 ccaccctcac tggccttctg cagcagggtt ctgggatgtt ttcagtggtc 8500 aaaatactct gtttagagca agggctcaga aaacagaaat actgtcatgg 8550 aggtgctgaa cacagggaag gtctggtaca tattggaaat tatgagcaga 8600 acaaatactc aactaaatgc acaaagtata aagtgtagcc atgtctagac 8650 accatgttgt atcagaataa tttttgtgcc aataaatgac atcagaattt 8700 taaacat 8707 gcggggaagg cgggcggtgg ggcagggggc ctgaagcggc ggtaccggtg 50 ctggcggcgg cagctgaggc cttggccgaa gccgcgcgaa cctcagggca 100 agatgcttgg aaccggacct gccgccgcca ccaccgctgc caccacatct 150 gcgtcctgca agcaatgtga agtggcctaa gcagtttgcc agagccggaa 200 tgaggaaacc agggccaaag ccgccaagga gctccagcac tatgtcacca 250 tggaactccg agagatgagt caagaggagt ctactcgctt ctatgaccaa 300 acatttttga ctgaaccatc attggtttcc agctcagatg ccaatgagag 350 atcttggcca gaaaggtggc tagctagcct cataggagtg gaaggtggga 400 atgccacccg aattggcaga tttgccaact atcttcggaa cctcctcccc 450 tccaatgacc cagttgtcat ggaaatggca tccaaggcca ttggccgtct 500 ggggacactt tgccatggca gtacgtggaa ttaccgctga tttgaggtga 550 agcgagccct ggaatggctg ggtgctgacc gcaatgaggg ccggagacat 600 gcagctgtcc tggttctccg tgagctggcc atcagcgtcc ctaccttctt 650 cttccagcaa gtgcaaccct tctttgacaa catttttgtg gccgtgtggg 700 accccaaaca ggccatccgt gagggagctg tagccgccct tcgtgcctgt 750 ctgattctca caacccagcg tgagccgaag gagatgcaga agcctcagtg 800 gtacaggcac acatttgaag aagcagagaa gggatttg at gagaccttgg 850 ccaaagagaa gggcatgaat cgggatgatc ggatccatgg agccttgttg 900 atccttaacg agctggtccg aatcagcagc atggagggag agcgtctgag 950 gaagaaatca agaagaaatg cacagcagca gctggtacac gacaagtact 1000 gcaaagatct catgggcttc ggaacaaaac ctcgtcacat tacccccttc 1050 accagtttcc aggctgtaca gccccagcag tcaaatgcct tggtggggct 1100 gctggggtac agctctcacc aaggcctcat gggatttggg acctccccca 1150 gtccagctaa gtccaccctg gtggagagcc ggtgttgcag agacttgatg 1200 gaggagaaat ttgatcaggt gtgccagtgg gtgctgaaat gcaggaatag 1250 caagaactcg ctgatccaaa tgacaatcct taatttgttg ccccgcttgg 1300 ctgcattccg accttctgcc ttcacagata cccagtatct ccaagatacc 1350 atgaaccatg tcctaagctg tgtcaagaag gagaaggaac gtacagcggc 1400 cttccaagcc ctggggctac tttctgtggc tgtgaggtct gagtttaagg 1450 tctatttgcc tcgcgtgctg gacatcatcc gagcggccct gcccccaaag 1500 ataagaggca gacttcgccc gaaggcaatg caggtggatg ccacagtctt 1550 cacttgcatc agcatgctgg ctcgagcaat ggggccaggc atccagcagg 1600 atatcaagga gctgctggag cccatgctgg cagtgggact aagccctgcc 1650 ctcactgc ag tgctctacga cctgagccgt cagattccac agctaaagaa 1700 ggacattcaa gatgggctac tgaaaatgct gtccctggtc cttatgcaca 1750 aaccccttcg ccacccaggc atgcccaagg gcctggccca tcagctggcc 1800 tctcctggcc tcacgaccct ccctgaggcc agcgatgtgg gcagcatcac 1850 tcttgccctc cgaacgcttg gcagctttga atttgaaggc cactctctga 1900 cccaatttgt tcgccactgt gcggatcatt tcctgaacag tgagcacaag 1950 gagatccgca tggaggctgc ccgcacctgc tcccgcctgc tcacaccctc 2000 catccacctc atcagtggcc atgctcatgt ggttagccag accgcagtgc 2050 aagtggtggc agatgtgctt agcaaactgc tcgtagttgg gataacagat 2100 cctgaccctg acattcgcta ctgtgtcttg gcgtccctgg acgagcgctt 2150 tgatgcacac ctggcccagg cggagaactt gcaggccttg tttgtggctc 2200 tgaatgacca ggtgtttgag atccgggagc tggccatctg cactgtgggc 2250 cgactcagta gcatgaaccc tgcctttgtc atgcctttcc tgcgcaagat 2300 gctcatccag attttgacag agttggagca ggaagaatca cagtgggatt 2350 aagagcagag tgcccgcatg ctggggcacc tggtctccaa tgccccccga 2400 ctcatccgcc cctacatgga gcctattctg aaggcattaa ttttgaaact 2450 gaaagatcca gaccctgatc caaacccagg tgtgatcaat aatgtcctgg 2500 caacaatagg agaattggca caggttagtg gcctggaaat gaggaaatgg 2550 gttgatgaac tttttattat catcatggac atgctccagg attcctcttt 2600 gttggccaaa aggcaggtgg ctctgtggac cctgggacag ttggtggcca 2650 gcactggcta tgtagtagag ccctacagga agtaccctac tttgcttgag 2700 attttctgaa gtgctactga gactgagcag aaccagggta cacgcagaga 2750 ggccatccgt gtgttagggc ttttaggggc tttggatcct tacaagcaca 2800 aagtgaacat tggcatgata gaccagtccc gggatgcctc tgctgtcagc 2850 ctgtcagaat ccaagtcaag tcaggattcc tctgactata gcactagtga 2900 aatgctggtc aacatgggaa acttgcctct ggatgagttc tacccagctg 2950 tgtccatggt ggccctgatg cggatcttcc gagaccagtc actctctcat 3000 tggttgtcca catcacacca ggccatcacc ttcatcttca agtccctggg 3050 actcaaatgt gtgcagttcc tgccccaggt catgcccacg ttccttaacg 3100 tcattcgagt ctgtgatggg gccatccggg aatttttgtt ccagcagctg 3150 ggaatgttgg tgtcctttgt gaagagccac atcagacctt atatggatga 3200 aatagtcacc ctcatgagag aattctgggt catgaacacc tcaattcaga 3250 gcacgatcat tcttctcatt gagcaaattg tggtagctct tgggggtgaa 3 300 tttaagctct acctgcccca gctgatccca cacatgctgc gtgtcttcat 3350 gcatgacaac agcccaggcc gcattgtctc tatcaagtta ctggctgcaa 3400 tccagctgtt tggcgccaac ctggatgact acctgcattt actgctgcct 3450 agttgtttga cctattgtta gctccactgc tgcccctgaa catctcgaaa 3500 ggcagcgcta gagactgtgg accgcctgac ggagtccctg gatttcactg 3550 actatgcctc ccggatcatt caccctattg ttcgaacact ggaccagagc 3600 ccagaactgc gctccacagc catggacacg ctgtcttcac ttgtttttca 3650 gctggggaag aagtaccaaa ttttcattcc aatggtgaat aaagttctgg 3700 tgcgacaccg aatcaatcat cagcgctatg atgtgctcat ctgcagaatt 3750 gtcaagggat acacacttgc tgatgaagag gaggatcctt tgatttacca 3800 gcatcggatg cttaggagtg gccaagggga tgcattggct agtggaccag 3850 tggaaacagg acccatgaag aaactgcacg tcagcaccat caacctccaa 3900 aaggcaaccg cctggggcgc tgccaggagg gtctccaaag atgactggct 3950 ggaatggctg agacggctga gcctggagct gctgaaggac tcatcatcgc 4000 cctccctgcg ctcctgctgg gccctggcac aggcctacaa cccgatggcc 4050 agggatctct tcaatgctgc atttgtgtcc tgctggtctg aactgaatga 4100 agatcaacag gatgagctc to tcagaagcat cgagttggcc ctcacctcac 4150 tgaagtcaca aagacatcgc cagaccctct taaacttggc tgaattcatg 4200 gaacacagtg acaagggccc cctgccactg agagatgaca atggcattgt 4250 tctgctgggt gagagagctg ccaagtgccg agcatatgcc aaagcactac 4300 actacaaaga actggagttc cagaaaggcc ccacccctgc cattctagaa 4350 gcattaataa tctctcatca taagctacag cagccggagg cagcggccgg 4400 tatgccatga agtgttagaa aacactttgg agagctggag atccaggcta 4450 cctggtatga gaaactgcac gagtgggagg atgcccttgt ggcctatgac 4500 acaccaacaa aagaaaatgg ggacgaccca gagctgatgc tgggccgcat 4550 gcgctgcctc gaggccttgg gggaatgggg tcaactccac cagcagtgct 4600 gtgaaaagtg gaccctggtt aatgatgaga cccaagccaa gatggcccgg 4650 atggctgctg cagctgcatg gggtttaggt cagtgggaca gcatggaaga 4700 atacacctgt atgatccctc gggacaccca tgatggggca ttttatagag 4750 ctgtgctggc actgcatcag gacctcttct ccttggcaca acagtgcatt 4800 gacaaggcca gggacctgct ttaactgcga ggatgctgaa tggcaggaga 4850 gagttacagt cgggcatatg gggccatggt ttcttgccac atgctgtccg 4900 agctggagga ggttatccag tacaaacttg tccccgagcg to cgagagatc 4950 tctggtggga atccgccaga gagactgcag ggctgccagc gtatcgtaga 5000 ggactggcag aaaatcctta tggtgcggtc ccttgtggtc agccctcatg 5050 aagacatgag aacctggctc aagtatgcaa gcctgtgcgg caagagtggc 5100 aggctggctc ttgctcataa aactttagtg ttgctcctgg gagttgatcc 5150 gtctcggcaa cttgaccatc ctctgccaac agttcaccct caggtgacct 5200 atgcctacat gaaaaacatg tggaagagtg cccgcaagat cgatgccttc 5250 cagcacatgc agcattttgt ccagaccatg cagcaacagg cccagcatgc 5300 catcgctact gaggaccagc agcataagca ggaactgcac aagctcatgg 5350 cccgatgctt cctgaaactt ggagagtggc agctgaatct acagggcatc 5400 caatccccaa aatgagagca agtgctgcag tactacagcg ccgccacaga 5450 agctggtaca gcacgaccgc aggcctggca tgcgtgggca gtgatgaact 5500 tcgaagctgt gctacactac aaacatcaga accaagcccg cgatgagaag 5550 aagaaactgc gtcatgccag cggggccaac atcaccaacg ccaccactgc 5600 ccaccaccac cgccaccacg gccgccactg tgccagcacc gagggcagca 5650 acagtgagag cgaggccgag agcaccgaga acagccccac cccatcgccg 5700 aggtcactga ctgcagaaga ggatctgtcc aaaaccctcc tgatgtacac 5750 ggtgcctg cc gtccagggct tcttccgttc catctccttg tcacgaggca 5800 acaacctcca ggatacactc agagttctca ccttatggtt tgattatggt 5850 atgtcaatga cactggccag ggccttagtg gagggggtga aagccatcca 5900 gattgatacc tggctacagg ttatacctca gctcattgca agaattgata 5950 cgcccagacc cttggtggga cgtctcattc accagcttct cacagacatt 6000 ggtcggtacc acccccaggc cctcatctac ccactgacag tggcttctaa 6050 gtctaccacg acagcccggc acaatgcagc caacaagatt ctgaagaaca 6100 tgtgtgagca cagcaacacc ctggtccagc aggccatgat ggtgagcgag 6150 gagctgatcc gagtggccat cctctggcat gagatgtggc atgaaggcct 6200 ggaagaggca tctcgtttgt actttgggga aaggaacgtg aaaggcatgt 6250 ttgaggtgct ggagcccttg catgctatga tggaacgggg cccccagact 6300 ctgaaggaaa catcctttaa tcaggcctat ggtcgagatt taatggaggc 6350 ccaagagtgg tgcaggaagt acatgaaatc agggaatgtc aaggacctca 6400 cccaagcctg ggacctctat tatcatgtgt tccgacgaat ctcaaagcag 6450 ctgcctcagc tcacatcctt agagctgcaa tatgtttccc caaaacttct 6500 gatgtgccgg gaccttgaat tggctgtgcc aggaacatat gaccccaacc 6550 agccaatcat tcgcattcag tccatagcac cgtctttgca agtcatcaca 6600 ggccccggaa tccaagcaga attgacactt atgggcagca acggacatga 6650 gtttgttttc cttctaaaag gccatgaaga tctgcgccag gatgagcgtg 6700 tgatgcagct cttcggcctg gttaacaccc tgacccaaca ttctggccaa 6750 aaaacctcag tctcttcgga catccagaga tacgctgtca tccctttatc 6800 gaccaactcg ggcctcattg gctgggttcc ccactgtgac acactgcacg 6850 ccctcatccg ggactacagg gagaagaaga agatccttct caacatcgag 6900 catcgcatca tgttgcggat ggctccggac tatgaccact tgactctgat 6950 gcagaaggtg gaggtgtttg agcatgccgt caataataca gctggggacg 7000 acctggccaa gctgctgtgg ctgaaaagcc ccagctccga ggtgtggttt 7050 gaccgaagaa ccaattatac ccgttcttta gcggtcatgt caatggttgg 7100 gtatatttta ggcctgggag atagacaccc atccaacctg atgctggacc 7150 gtctgagtgg gaagatcctg cacattgact ttggggactg ctttgaggtt 7200 gctatgaccc gagagaagtt tccagagaag attccattta gactaacaag 7250 aatgttgacc aatgctatgg aggttacagg cctggatggc aactacagaa 7300 tcacatgcca cacagtgatg gaggtgctgc gagagcacaa ggacagtgtc 7350 atggccgtgc tggaagcctt tgtctatgac cccttgctga actggaggct 7 400 gatggacaca aataccaaag gcaacaagcg atcccgaacg aggacggatt 7450 tggccagtca cctactctgc gtcgaaattt tggacggtgt ggaacttgga 7500 gagccagccc ataagaaaac ggggaccaca gtgccagaat ctattcattc 7550 tttcattgga gacggtttgg tgaaaccaga ggccctaaat aagaaagcta 7600 tccagattat taacagggtt cgagataagc tcactggtcg ggacttctct 7650 catgatgaca ctttggatgt tccaacgcaa gttgagctgc tcatcaaaca 7700 agcgacatcc catgaaaacc tctgccagtg ctatattggc tggtgccctt 7750 tctggtaact ggaggcccag atgtgcccat cacgtttttt ctgaggcttt 7800 tgtactttag taaatgcttc cactaaactg aaaccatggt gagaaagttt 7850 aatattttga gactttgtta aatgtaaatg aaaagaacta ctgtatatta 7900 aaagttggtt tgaaccaact ttctagctgc tgttgaagaa tatattgtca 7950 gaaacacaag gcttgatttg cagtgaaaca gttcccagga tagtaatacc 8000 acgtaaatca agccattcat tttggggaac agaagatcca taactttaga 8050 aatacgggtt ttgacttaac tcacaagaga actcatcata agtacttgct 8100 tgacctagtt gatggaagaa gctcctctca agcaaactca acatgggtac 8150 gaagcctcag gcacagccaa gtcgtggaga acatggatta ggatcctaga 8200 acagaaga ctgtaaagac tg ctgacctcac ccctgccacc tatcccaaga 8250 cctcactggt ctgtggacag cagcagaaat taggccaaaa gtttgcaaga 8300 tgagtacaaa aggtctgtct tccatcagac ccagtgatgc tgcgactcac 8350 acgcttcaat tcaagacctg accgctagta gggaggttta ttcagatcgc 8400 tggcagcctc ggctgagcag atgcacagag gggatcactg tgcagtggga 8450 ccaccctcac tggccttctg cagcagggtt ctgggatgtt ttcagtggtc 8500 gtttagagca aaaatactct agggctcaga aaacagaaat actgtcatgg 8550 aggtgctgaa cacagggaag gtctggtaca tattggaaat tatgagcaga 8600 aactaaatgc acaaatactc acaaagtata aagtgtagcc atgtctagac 8650 accatgttgt atcagaataa tttttgtgcc aataaatgac atcagaattt 8700 taaacat 8707

<210> 9 <210> 9

<211> 5822 <211> 5822

<212> ADN <212> DNA

<213> Homo sapiens <213> Homo sapiens

<400> 9 <400> 9

actgagtccc gggaccccgg gagagcggtc aatgtgtggt cgctgcgttt 50 actgagtccc gggaccccgg gagagcggtc aatgtgtggt cgctgcgttt 50

cctctgcctg cgccgggcat cacttgcgcg ccgcagaaag tccgtctggc 100 cctctgcctg cgccgggcat cacttgcgcg ccgcagaaag tccgtctggc 100

agcctggata tcctctccta ccggcacccg cagacgcccc tgcagccgcg 150 agcctggata tcctctccta ccggcacccg cagacgcccc tgcagccgcg 150

gtcggcgccc gggctcccta gccctgtgcg ctcaactgtc ctgcgctgcg 200 gtcggcgccc gggctcccta gccctgtgcg ctcaactgtc ctgcgctgcg 200

gggtgccgcg agttccacct ccgcgcctcc ttctctagac aggcgctggg 250 gggtgccgcg agttccacct ccgcgcctcc ttctctagac aggcgctggg 250

agaaagaacc ggctcccgag ttctgggcat ttcgcccggc tcgaggtgca 300 agaaagaacc ggctcccgag ttctgggcat ttcgcccggc tcgaggtgca 300

ggatgcagag caaggtgctg ctggccgtcg ccctgtggct ctgcgtggag 350 ggatgcagag caaggtgctg ctggccgtcg ccctgtggct ctgcgtggag 350

acccgggccg cctctgtggg tttgcctagt gtttctcttg atctgcccag 400 acccgggccg cctctgtggg tttgcctagt gtttctcttg atctgcccag 400

gctcagcata caaaaagaca tacttacaat taaggctaat acaactcttc 450 gctcagcata caaaaagaca tacttacaat taaggctaat acaactcttc 450

aaattacttg caggggacag agggacttgg actggctttg gcccaataat 500 aaattacttg caggggacag agggacttgg actggctttg gcccaataat 500

cagagtggca gtgagcaaag ggtggaggtg actgagtgca gcgatggcct 550 cagagtggca gtgagcaaag ggtggaggtg actgagtgca gcgatggcct 550

cttctgtaag acactcacaa ttccaaaagt gatcggaaat gacactggag 600 cttctgtaag acactcacaa ttccaaaagt gatcggaaat gacactggag 600

cctacaagtg cttctaccgg gaaactgact tggcctcggt catttatgtc 650 cctacaagtg cttctaccgg gaaactgact tggcctcggt catttatgtc 650

tatgttcaag attacagatc tccatttatt gcttctgtta gtgaccaaca 700 tatgttcaag attacagatc tccatttatt gcttctgtta gtgaccaaca 700

tggagtcgtg tacattactg agaacaaaaa caaaactgtg gtgattccat 750 tggagtcgtg tacattactg agaacaaaaa caaaactgtg gtgattccat 750

gtctcgggtc catttcaaat ctcaacgtgt cactttgtgc aagataccca 800 gtctcgggtc catttcaaat ctcaacgtgt cactttgtgc aagataccca 800

gaaaagagat ttgttcctga tggtaacaga atttcctggg acagcaagaa 850 gaaaagagat ttgttcctga tggtaacaga atttcctggg acagcaagaa 850

gggctttact attcccagct acatgatcag ctatgctggc atggtcttct 900 gggctttact attcccagct acatgatcag ctatgctggc atggtcttct 900

gtgaagcaaa aattaatgat gaaagttacc agtctattat gtacatagtt 950 gtgaagcaaa aattaatgat gaaagttacc agtctattat gtacatagtt 950

gtcgttgtag ggtataggat ttatgatgtg gttctgagtc cgtctcatgg 1000 gtcgttgtag ggtataggat ttatgatgtg gttctgagtc cgtctcatgg 1000

aattgaacta tctgttggag aaaagcttgt cttaaattgt acagcaagaa 1050 aattgaacta tctgttggag aaaagcttgt cttaaattgt acagcaagaa 1050

ctgaactaaa tgtggggatt gacttcaact gggaataccc ttcttcgaag 1100 ctgaactaaa tgtggggatt gacttcaact gggaataccc ttcttcgaag 1100

catcagcata agaaacttgt aaaccgagac ctaaaaaccc agtctgggag 1150 catcagcata agaaacttgt aaaccgagac ctaaaaaccc agtctgggag 1150

tgagatgaag aaatttttga gcaccttaac tatagatggt gtaacccgga 1200 tgagatgaag aaatttttga gcaccttaac tatagatggt gtaacccgga 1200

gtgaccaagg attgtacacc tgtgcagcat ccagtgggct gatgaccaag 1250 gtgaccaagg attgtacacc tgtgcagcat ccagtgggct gatgaccaag 1250

aagaacagca catttgtcag ggtccatgaa aaaccttttg ttgcttttgg 1300 aagaacagca catttgtcag ggtccatgaa aaaccttttg ttgcttttgg 1300

aagtggcatg gaatctctgg tggaagccac ggtgggggag cgtgtcagaa 1350 aagtggcatg gaatctctgg tggaagccac ggtgggggag cgtgtcagaa 1350

tccctgcgaa gtaccttggt tacccacccc cagaaataaa atggtataaa 1400 tccctgcgaa gtaccttggt tacccacccc cagaaataaa atggtataaa 1400

aatggaatac cccttgagtc caatcacaca attaaagcgg ggcatgtact 1450 gacgattatg gaagtgagtg aaagagacac aggaaattac actgtcatcc 1500 ttaccaatcc catttcaaag gagaagcaga gccatgtggt ctctctggtt 1550 gtgtatgtcc caccccagat tggtgagaaa tctctaatct ctcctgtgga 1600 ttcctaccag tacggcacca ctcaaacgct gacatgtacg gtctatgcca 1650 ttcctccccc gcatcacatc cactggtatt ggcagttgga ggaagagtgc 1700 gccaacgagc ccagccaagc tgtctcagtg acaaacccat acccttgtga 1750 agaatggaga agtgtggagg acttccaggg aggaaataaa attgaagtta 1800 ataaaaatca atttgctcta attgaaggaa aaaacaaaac tgtaagtacc 1850 cttgttatcc aagcggcaaa tgtgtcagct ttgtacaaat gtgaagcggt 1900 caacaaagtc gggagaggag agagggtgat ctccttccac gtgaccaggg 1950 gtcctgaaat tactttgcaa cctgacatgc agcccactga gcaggagagc 2000 gtgtctttgt ggtgcactgc agacagatct acgtttgaga acctcacatg 2050 gtacaagctt ggcccacagc ctctgccaat ccatgtggga gagttgccca 2100 cacctgtttg caagaacttg gatactcttt ggaaattgaa tgccaccatg 2150 ttctctaata gcacaaatga cattttgatc atggagctta agaatgcatc 2200 cttgcaggac caaggagact atgtctgcct tgctcaagac aggaagacca 2250 agaaaagaca ttgcgtggtc aggcagctca cagtcctaga gcgtgtggca 2300 cccacgatca caggaaacct ggagaatcag acgacaagta ttggggaaag 2350 catcgaagtc tcatgcacgg catctgggaa tccccctcca cagatcatgt 2400 ggtttaaaga taatgagacc cttgtagaag actcaggcat tgtattgaag 2450 gatgggaacc ggaacctcac tatccgcaga gtgaggaagg aggacgaagg 2500 cctctacacc tgccaggcat gcagtgttct tggctgtgca aaagtggagg 2550 catttttcat aatagaaggt gcccaggaaa agacgaactt ggaaatcatt 2600 attctagtag gcacggcggt gattgccatg ttcttctggc tacttcttgt 2650 catcatccta cggaccgtta agcgggccaa tggaggggaa ctgaagacag 2700 gctacttgtc catcgtcatg gatccagatg aactcccatt ggatgaacat 2750 tgtgaacgac tgccttatga tgccagcaaa tgggaattcc ccagagaccg 2800 gctgaagcta ggtaagcctc ttggccgtgg tgcctttggc caagtgattg 2850 aagcagatgc ctttggaatt gacaagacag caacttgcag gacagtagca 2900 gtcaaaatgt tgaaagaagg agcaacacac agtgagcatc gagctctcat 2950 gtctgaactc aagatcctca ttcatattgg tcaccatctc aatgtggtca 3000 accttctagg tgcctgtacc aagccaggag ggccactcat ggtgattgtg 3050 gaattctgca aatttggaaa cctgtccact tacctgagga gcaagagaaa 3100 tgaatttgtc ccctacaaga ccaaaggggc acgattccgt caagggaaag 3150 actacgttgg agcaatccct gtggatctga aacggcgctt ggacagcatc 3200 accagtagcc agagctcagc cagctctgga tttgtggagg agaagtccct 3250 cagtgatgta gaagaagagg aagctcctga agatctgtat aaggacttcc 3300 tgaccttgga gcatctcatc tgttacagct tccaagtggc taagggcatg 3350 gagttcttgg catcgcgaaa gtgtatccac agggacctgg cggcacgaaa 3400 tatcctctta tcggagaaga acgtggttaa aatctgtgac tttggcttgg 3450 cccgggatat ttataaagat ccagattatg tcagaaaagg agatgctcgc 3500 ctccctttga aatggatggc cccagaaaca atttttgaca gagtgtacac 3550 aatccagagt gacgtctggt cttttggtgt tttgctgtgg gaaatatttt 3600 ccttaggtgc ttctccatat cctggggtaa agattgatga agaattttgt 3650 aggcgattga aagaaggaac tagaatgagg gcccctgatt atactacacc 3700 agaaatgtac cagaccatgc tggactgctg gcacggggag cccagtcaga 3750 gacccacgtt ttcagagttg gtggaacatt tgggaaatct cttgcaagct 3800 aatgctcagc aggatggcaa agactacatt gttcttccga tatcagagac 3850 tttgagcatg gaagaggatt ctggactctc tctgcctacc tcacctgttt 3900 cctgtatgga ggaggaggaa gtatgtgacc ccaaattcca ttatgacaac 3950 acagcaggaa tcagtcagta tctgcagaac agtaagcgaa agagccggcc 4000 tgtgagtgta aaaacatttg aagatatccc gttagaagaa ccagaagtaa 4050 aagtaatccc agatgacaac cagacggaca gtggtatggt tcttgcctca 4100 gaagagctga aaactttgga agacagaacc aaattatctc catcttttgg 4150 tggaatggtg cccagcaaaa gcagggagtc tgtggcatct gaaggctcaa 4200 accagacaag cggctaccag tccggatatc actccgatga cacagacacc 4250 accgtgtact ccagtgagga agcagaactt ttaaagctga tagagattgg 4300 agtgcaaacc ggtagcacag cccagattct ccagcctgac tcggggacca 4350 cactgagctc tcctcctgtt taaaaggaag catccacacc cccaactcct 4400 ggacatcaca tgagaggtgc tgctcagatt ttcaagtgtt gttctttcca 4450 ccagcaggaa gtagccgcat ttgattttca tttcgacaac agaaaaagga 4500 cctcggactg cagggagcca gtcttctagg catatcctgg aagaggcttg 4550 tgacccaaga atgtgtctgt gtcttctccc agtgttgacc tgatcctctt 4600 tttcattcat ttaaaaagca tttatcatgc cccctgctgc gggtctcacc 4650 atgggtttag aacaaagacg ttcaagaaat ggccccatcc tcaaagaagt 4700 agcagtacct ggggagctga cacttctgta aaactagaag ataaaccagg 4750 caatgtaagt gttcgaggtg ttgaagatgg gaaggatttg cagggctgag 4800 tctatccaag aggctttgtt taggacgtgg gtcccaagcc aagccttaag 4850 tgtggaattc ggattgatag aaaggaagac taacgttacc ttgctttgga 4900 gagtactgga gcctgcaaat gcattgtgtt tgctctggtg gaggtgggca 4950 tggggtctgt tctgaaatgt aaagggttca gacggggttt ctggttttag 5000 aaggttgcgt gttcttcgag ttgggctaaa gtagagttcg ttgtgctgtt 5050 tctgactcct aatgagagtt ccttccagac cgttacgtgt ctcctggcca 5100 agccccagga aggaaatgat gcagctctgg ctccttgtct cccaggctga 5150 tcctttattc agaataccac aaagaaagga cattcagctc aaggctccct 5200 gccgtgttga agagttctga ctgcacaaac cagcttctgg tttcttctgg 5250 aatgaatacc ctcatatctg tcctgatgtg atatgtctga gactgaatgc 5300 gggaggttca atgtgaagct gtgtgtggtg tcaaagtttc aggaaggatt 5350 ttaccctttt gttcttcccc ctgtccccaa cccactctca ccccgcaacc 5400 catcagtatt ttagttattt ggcctctact ccagtaaacc tgattgggtt 5450 tgttcactct ctgaatgatt attagccaga cttcaaaatt attttatagc 5500 ccaaattata acatctattg tattatttag acttttaaca tatagagcta 5550 tttctactga tttttgccct tgttctgtcc tttttttcaa aaaagaaaat 5600 gtgttttttg tttggtacca tagtgtgaaa tgctgggaac aatgactata 5650 agacatgcta tggcacatat atttatagtc tgtttatgta gaaacaaatg 5700 taatatatta aagccttata tataatgaac tttgtactat tcacattttg 5750 tatcagtatt atgtagcata acaaaggtca taatgctttc agcaattgat 5800 gtcattttat taaagaacat tg 5822 aatggaatac cccttgagtc caatcacaca attaaagcgg ggcatgtact 1450 gacgattatg gaagtgagtg aaagagacac aggaaattac actgtcatcc 1500 ttaccaatcc catttcaaag gagaagcaga gccatgtggt ctctctggtt 1550 gtgtatgtcc caccccagat tggtgagaaa tctctaatct ctcctgtgga 1600 ttcctaccag tacggcacca ctcaaacgct gacatgtacg gtctatgcca 1650 ttcctccccc gcatcacatc cactggtatt ggcagttgga ggaagagtgc 1700 gccaacgagc ccagccaagc tgtctcagtg acaaacccat acccttgtga 1750 agaatggaga agtgtggagg acttccaggg aggaaataaa attgaagtta 1800 atttgctcta ataaaaatca attgaaggaa aaaacaaaac tgtaagtacc 1850 cttgttatcc aagcggcaaa tgtgtcagct ttgtacaaat gtgaagcggt 1900 caacaaagtc gggagaggag agagggtgat ctccttccac gtgaccaggg 1950 gtcctgaaat tactttgcaa cctgacatgc agcccactga gcaggagagc 2000 gtgtctttgt ggtgcactgc agacagatct acgtttgaga acctcacatg 2050 gtacaagctt ggcccacagc ctctgccaat gagttgccca ccatgtggga 2100 cacctgtttg caagaacttg gatactcttt ggaaattgaa tgccaccatg ttctctaata 2150 gcacaaatga cattttgatc atggagctta agaatgcatc caaggagact at 2200 cttgcaggac gtctgcct tgctcaagac aggaagacca 2250 agaaaagaca aggcagctca ttgcgtggtc cagtcctaga gcgtgtggca 2300 cccacgatca caggaaacct ggagaatcag acgacaagta ttggggaaag 2350 catcgaagtc tcatgcacgg tccccctcca catctgggaa cagatcatgt 2400 ggtttaaaga taatgagacc cttgtagaag actcaggcat tgtattgaag 2450 gatgggaacc ggaacctcac tatccgcaga gtgaggaagg aggacgaagg 2500 cctctacacc tgccaggcat gcagtgttct tggctgtgca aaagtggagg 2550 catttttcat aatagaaggt gcccaggaaa agacgaactt ggaaatcatt 2600 attctagtag gcacggcggt gattgccatg ttcttctggc tacttcttgt 2650 cggaccgtta catcatccta tggaggggaa agcgggccaa ctgaagacag 2700 gctacttgtc catcgtcatg gatccagatg aactcccatt ggatgaacat 2750 tgtgaacgac tgccttatga tgccagcaaa tgggaattcc ccagagaccg 2800 gctgaagcta ggtaagcctc ttggccgtgg tgcctttggc caagtgattg 2850 aagcagatgc ctttggaatt gacaagacag caacttgcag gacagtagca 2900 gtcaaaatgt tgaaagaagg agcaacacac agtgagcatc gagctctcat 2950 aagatcctca gtctgaactc ttcatattgg tcaccatctc aatgtggtca 3000 accttctagg tgcctgtacc aagccaggag ggccactcat ggtg attgtg 3050 aatttggaaa gaattctgca tacctgagga cctgtccact gcaagagaaa 3100 tgaatttgtc ccctacaaga ccaaaggggc acgattccgt caagggaaag 3150 actacgttgg agcaatccct gtggatctga aacggcgctt ggacagcatc 3200 accagtagcc agagctcagc cagctctgga tttgtggagg agaagtccct 3250 cagtgatgta gaagaagagg aagctcctga agatctgtat aaggacttcc 3300 tgaccttgga gcatctcatc tgttacagct tccaagtggc taagggcatg 3350 gagttcttgg catcgcgaaa gtgtatccac agggacctgg cggcacgaaa 3400 tcggagaaga tatcctctta acgtggttaa aatctgtgac tttggcttgg 3450 cccgggatat ttataaagat ccagattatg tcagaaaagg agatgctcgc 3500 ctccctttga aatggatggc atttttgaca cccagaaaca gagtgtacac 3550 aatccagagt gacgtctggt cttttggtgt tttgctgtgg gaaatatttt 3600 ccttaggtgc ttctccatat cctggggtaa agattgatga agaattttgt 3650 aggcgattga aagaaggaac tagaatgagg gcccctgatt atactacacc 3700 agaaatgtac cagaccatgc tggactgctg gcacggggag cccagtcaga 3750 gacccacgtt ttcagagttg gtggaacatt tgggaaatct cttgcaagct 3800 aatgctcagc aggatggcaa agactacatt gttcttccga tatcagagac 3850 tttgagcatg gaagaggatt ctggactctc tctgcctacc tcacctgttt 3900 ggaggaggaa cctgtatgga gtatgtgacc ccaaattcca ttatgacaac 3950 tcagtcagta acagcaggaa tctgcagaac agtaagcgaa agagccggcc 4000 tgtgagtgta aaaacatttg aagatatccc gttagaagaa ccagaagtaa 4050 aagtaatccc agatgacaac cagacggaca tcttgcctca gtggtatggt 4100 aaactttgga gaagagctga agacagaacc aaattatctc catcttttgg 4150 tggaatggtg cccagcaaaa gcagggagtc tgtggcatct gaaggctcaa 4200 accagacaag cggctaccag tccggatatc actccgatga cacagacacc 4250 accgtgtact ccagtgagga agcagaactt ttaaagctga tagagattgg 4300 agtgcaaacc ggtagcacag cccagattct ccagcctgac tcggggacca 4350 cactgagctc tcctcctgtt taaaaggaag catccacacc cccaactcct 4400 ggacatcaca tgagaggtgc tgctcagatt ttcaagtgtt gttctttcca 4450 ccagcaggaa gtagccgcat ttgattttca tttcgacaac agaaaaagga 4500 cagggagcca cctcggactg gtcttctagg catatcctgg aagaggcttg 4550 tgacccaaga atgtgtctgt gtcttctccc agtgttgacc tgatcctctt 4600 tttcattcat ttaaaaagca tttatcatgc cccctgctgc gggtctcacc 4650 atgggtttag aacaaagacg ttcaagaaat gg ccccatcc tcaaagaagt 4700 ggggagctga agcagtacct cacttctgta aaactagaag ataaaccagg 4750 caatgtaagt gttcgaggtg ttgaagatgg gaaggatttg cagggctgag 4800 tctatccaag aggctttgtt taggacgtgg gtcccaagcc aagccttaag 4850 tgtggaattc ggattgatag aaaggaagac taacgttacc ttgctttgga 4900 gagtactgga gcctgcaaat gcattgtgtt tgctctggtg gaggtgggca 4950 tggggtctgt tctgaaatgt aaagggttca gacggggttt ctggttttag 5000 aaggttgcgt gttcttcgag ttgggctaaa gtagagttcg ttgtgctgtt 5050 tctgactcct aatgagagtt ccttccagac cgttacgtgt ctcctggcca 5100 agccccagga aggaaatgat gcagctctgg ctccttgtct cccaggctga 5150 tcctttattc agaataccac aaagaaagga cattcagctc aaggctccct 5200 agagttctga gccgtgttga ctgcacaaac cagcttctgg tttcttctgg 5250 aatgaatacc ctcatatctg tcctgatgtg atatgtctga gactgaatgc 5300 gggaggttca atgtgaagct gtgtgtggtg tcaaagtttc aggaaggatt 5350 ttaccctttt gttcttcccc ctgtccccaa cccactctca ccccgcaacc 5400 catcagtatt ttagttattt ggcctctact ccagtaaacc tgattgggtt 5450 tgttcactct ctgaatgatt attagccaga cttcaaaatt attttatagc 5500 ccaaattata acatctattg tattatttag acttttaaca tatagagcta 5550 tttctactga tttttgccct tgttctgtcc tttttttcaa aaaagaaaat 5600 tttggtacca gtgttttttg tagtgtgaaa tgctgggaac aatgactata 5650 agacatgcta tggcacatat atttatagtc tgtttatgta gaaacaaatg 5700 aagccttata taatatatta tataatgaac tttgtactat tcacattttg 5750 atgtagcata tatcagtatt acaaaggtca taatgctttc agcaattgat 5800 gtcattttat taaagaacat tg 5822

<210> 10 <210> 10

<211> 4632 <211> 4632

<212> ADN <212> DNA

<213> Homo sapiens <213> Homo sapiens

<400> 10 <400> 10

gccctcgccg cccgcggcgc cccgagcgct ttgtgagcag atgcggagcc 50 gccctcgccg cccgcggcgc cccgagcgct ttgtgagcag atgcggagcc 50

gagtggaggg cgcgagccag atgcggggcg acagctgact tgctgagagg 100 gagtggaggg cgcgagccag atgcggggcg acagctgact tgctgagagg 100

aggcggggag gcgcggagcg cgcgtgtggt ccttgcgccg ctgacttctc 150 aggcggggag gcgcggagcg cgcgtgtggt ccttgcgccg ctgacttctc 150

cactggttcc tgggcaccga aagataaacc tctcataatg aaggcccccg 200 cactggttcc tgggcaccga aagataaacc tctcataatg aaggcccccg 200

ctgtgcttgc acctggcatc ctcgtgctcc tgtttacctt ggtgcagagg 250 ctgtgcttgc acctggcatc ctcgtgctcc tgtttacctt ggtgcagagg 250

agcaatgggg agtgtaaaga ggcactagca aagtccgaga tgaatgtgaa 300 agcaatgggg agtgtaaaga ggcactagca aagtccgaga tgaatgtgaa 300

tatgaagtat cagcttccca acttcaccgc ggaaacaccc atccagaatg 350 tatgaagtat cagcttccca acttcaccgc ggaaacaccc atccagaatg 350

tcattctaca tgagcatcac attttccttg gtgccactaa ctacatttat 400 tcattctaca tgagcatcac attttccttg gtgccactaa ctacatttat 400

gttttaaatg aggaagacct tcagaaggtt gctgagtaca agactgggcc 450 gttttaaatg aggaagacct tcagaaggtt gctgagtaca agactgggcc 450

tgtgctggaa cacccagatt gtttcccatg tcaggactgc agcagcaaag 500 tgtgctggaa cacccagatt gtttcccatg tcaggactgc agcagcaaag 500

ccaatttatc aggaggtgtt tggaaagata acatcaacat ggctctagtt 550 gtcgacacct actatgatga tcaactcatt agctgtggca gcgtcaacag 600 agggacctgc cagcgacatg tctttcccca caatcatact gctgacatac 650 agtcggaggt tcactgcata ttctccccac agatagaaga gcccagccag 700 tgtcctgact gtgtggtgag cgccctggga gccaaagtcc tttcatctgt 750 aaaggaccgg ttcatcaact tctttgtagg caataccata aattcttctt 800 atttcccaga tcatccattg cattcgatat cagtgagaag gctaaaggaa 850 acgaaagatg gttttatgtt tttgacggac cagtcctaca ttgatgtttt 900 acctgagttc agagattctt accccattaa gtatgtccat gcctttgaaa 950 gcaacaattt tatttacttc ttgacggtcc aaagggaaac tctagatgct 1000 cagacttttc acacaagaat aatcaggttc tgttccataa actctggatt 1050 gcattcctac atggaaatgc ctctggagtg tattctcaca gaaaagagaa 1100 aaaagagatc cacaaagaag gaagtgttta atatacttca ggctgcgtat 1150 gtcagcaagc ctggggccca gcttgctaga caaataggag ccagcctgaa 1200 tgatgacatt cttttcgggg tgttcgcaca aagcaagcca gattctgccg 1250 aaccaatgga tcgatctgcc atgtgtgcat tccctatcaa atatgtcaac 1300 gacttcttca acaagatcgt caacaaaaac aatgtgagat gtctccagca 1350 tttttacgga cccaatcatg agcactgctt taataggaca cttctgagaa 1400 attcatcagg ctgtgaagcg cgccgtgatg aatatcgaac agagtttacc 1450 acagctttgc agcgcgttga cttattcatg ggtcaattca gcgaagtcct 1500 cttaacatct atatccacct tcattaaagg agacctcacc atagctaatc 1550 ttgggacatc agagggtcgc ttcatgcagg ttgtggtttc tcgatcagga 1600 ccatcaaccc ctcatgtgaa ttttctcctg gactcccatc cagtgtctcc 1650 agaagtgatt gtggagcata cattaaacca aaatggctac acactggtta 1700 tcactgggaa gaagatcacg aagatcccat tgaatggctt gggctgcaga 1750 catttccagt cctgcagtca atgcctctct gccccaccct ttgttcagtg 1800 tggctggtgc cacgacaaat gtgtgcgatc ggaggaatgc ctgagcggga 1850 catggactca acagatctgt ctgcctgcaa tctacaaggt tttcccaaat 1900 agtgcacccc ttgaaggagg gacaaggctg accatatgtg gctgggactt 1950 tggatttcgg aggaataata aatttgattt aaagaaaact agagttctcc 2000 ttggaaatga gagctgcacc ttgactttaa gtgagagcac gatgaataca 2050 ttgaaatgca cagttggtcc tgccatgaat aagcatttca atatgtccat 2100 aattatttca aatggccacg ggacaacaca atacagtaca ttctcctatg 2150 tggatcctgt aataacaagt atttcgccga aatacggtcc tatggctggt 2200 ggcactttac ttactttaac tggaaattac ctaaacagtg ggaattctag 2250 acacatttca attggtggaa aaacatgtac tttaaaaagt gtgtcaaaca 2300 gtattcttga atgttatacc ccagcccaaa ccatttcaac tgagtttgct 2350 gttaaattga aaattgactt agccaaccga gagacaagca tcttcagtta 2400 ccgtgaagat cccattgtct atgaaattca tccaaccaaa tcttttatta 2450 gtacttggtg gaaagaacct ctcaacattg tcagttttct attttgcttt 2500 gccagtggtg ggagcacaat aacaggtgtt gggaaaaacc tgaattcagt 2550 tagtgtcccg agaatggtca taaatgtgca tgaagcagga aggaacttta 2600 cagtggcatg tcaacatcgc tctaattcag agataatctg ttgtaccact 2650 ccttccctgc aacagctgaa tctgcaactc cccctgaaaa ccaaagcctt 2700 tttcatgtta gatgggatcc tttccaaata ctttgatctc atttatgtac 2750 ataatcctgt gtttaagcct tttgaaaagc cagtgatgat ctcaatgggc 2800 aatgaaaatg tactggaaat taagggaaat gatattgacc ctgaagcagt 2850 taaaggtgaa gtgttaaaag ttggaaataa gagctgtgag aatatacact 2900 tacattctga agccgtttta tgcacggtcc ccaatgacct gctgaaattg 2950 aacagcgagc taaatataga gtggaagcaa gcaatttctt caaccgtcct 3000 tggaaaagta atagttcaac cagatcagaa tttcacagga ttgattgctg 3050 gtgttgtctc aatatcaaca gcactgttat tactacttgg gtttttcctg 3100 tggctgaaaa agagaaagca aattaaagat ctgggcagtg aattagttcg 3150 ctacgatgca agagtacaca ctcctcattt ggataggctt gtaagtgccc 3200 gaagtgtaag cccaactaca gaaatggttt caaatgaatc tgtagactac 3250 cgagctactt ttccagaaga tcagtttcct aattcatctc agaacggttc 3300 atgccgacaa gtgcagtatc ctctgacaga catgtccccc atcctaacta 3350 gtggggactc tgatatatcc agtccattac tgcaaaatac tgtccacatt 3400 gacctcagtg ctctaaatcc agagctggtc caggcagtgc agcatgtagt 3450 gattgggccc agtagcctga ttgtgcattt caatgaagtc ataggaagag 3500 ggcattttgg ttgtgtatat catgggactt tgttggacaa tgatggcaag 3550 aaaattcact gtgctgtgaa atccttgaac agaatcactg acataggaga 3600 agtttcccaa tttctgaccg agggaatcat catgaaagat tttagtcatc 3650 ccaatgtcct ctcgctcctg ggaatctgcc tgcgaagtga agggtctccg 3700 ctggtggtcc taccatacat gaaacatgga gatcttcgaa atttcattcg 3750 aaatgagact cataatccaa ctgtaaaaga tcttattggc tttggtcttc 3800 aagtagccaa aggcatgaaa tatcttgcaa gcaaaaagtt tgtccacaga 3850 gacttggctg caagaaactg tatgctggat gaaaaattca cagtcaaggt 3900 tgctgatttt ggtcttgcca gagacatgta tgataaagaa tactatagtg 3950 tacacaacaa aacaggtgca aagctgccag tgaagtggat ggctttggaa 4000 agtctgcaaa ctcaaaagtt taccaccaag tcagatgtgt ggtcctttgg 4050 cgtgctcctc tgggagctga tgacaagagg agccccacct tatcctgacg 4100 taaacacctt tgatataact gtttacttgt tgcaagggag aagactccta 4150 caacccgaat actgcccaga ccccttatat gaagtaatgc taaaatgctg 4200 gcaccctaaa gccgaaatgc gcccatcctt ttctgaactg gtgtcccgga 4250 tatcagcgat cttctctact ttcattgggg agcactatgt ccatgtgaac 4300 gctacttatg tgaacgtaaa atgtgtcgct ccgtatcctt ctctgttgtc 4350 atcagaagat aacgctgatg atgaggtgga cacacgacca gcctccttct 4400 gggagacatc atagtgctag tactatgtca aagcaacagt ccacactttg 4450 tccaatggtt ttttcactgc ctgaccttta aaaggccatc gatattcttt 4500 gctcttgcca aaattgcact attataggac ttgtattgtt atttaaatta 4550 ctggattcta aggaatttct tatctgacag agcatcagaa ccagaggctt 4600 ggtcccacag gccacggacc aatggcctgc ag 4632 ccaatttatc aggaggtgtt tggaaagata acatcaacat ggctctagtt 550 gtcgacacct actatgatga tcaactcatt agctgtggca gcgtcaacag 600 agggacctgc cagcgacatg tctttcccca caatcatact gctgacatac 650 agtcggaggt tcactgcata ttctccccac agatagaaga gcccagccag 700 tgtcctgact gtgtggtgag cgccctggga gccaaagtcc tttcatctgt 750 aaaggaccgg ttcatcaact tctttgtagg caataccata aattcttctt 800 atttcccaga tcatccattg cattcgatat cagtgagaag gctaaaggaa 850 acgaaagatg gttttatgtt tttgacggac cagtcctaca ttgatgtttt 900 acctgagttc agagattctt accccattaa gtatgtccat gcctttgaaa 950 gcaacaattt tatttacttc ttgacggtcc aaagggaaac tctagatgct 1000 cagacttttc acacaagaat aatcaggttc tgttccataa actctggatt 1050 gcattcctac atggaaatgc ctctggagtg tattctcaca gaaaagagaa 1100 aaaagagatc cacaaagaag gaagtgttta atatacttca ggctgcgtat 1150 ctggggccca gtcagcaagc gcttgctaga caaataggag ccagcctgaa 1200 tgatgacatt cttttcgggg tgttcgcaca aagcaagcca gattctgccg 1250 aaccaatgga tcgatctgcc atgtgtgcat tccctatcaa atatgtcaac 1300 acaagatcgt gacttcttca caacaaaaac aatgtgagat gtctccagca 1350 tttttacgga cccaatcatg agcactgctt taataggaca cttctgagaa 1400 attcatcagg ctgtgaagcg cgccgtgatg aatatcgaac agagtttacc 1450 agcgcgttga acagctttgc cttattcatg ggtcaattca gcgaagtcct 1500 cttaacatct atatccacct tcattaaagg agacctcacc atagctaatc 1550 ttgggacatc agagggtcgc ttcatgcagg ttgtggtttc tcgatcagga 1600 ccatcaaccc ctcatgtgaa ttttctcctg gactcccatc cagtgtctcc 1650 gtggagcata agaagtgatt cattaaacca aaatggctac acactggtta 1700 tcactgggaa gaagatcacg aagatcccat tgaatggctt gggctgcaga 1750 catttccagt cctgcagtca atgcctctct gccccaccct ttgttcagtg 1800 tggctggtgc cacgacaaat gtgtgcgatc ggaggaatgc ctgagcggga 1850 catggactca acagatctgt ctgcctgcaa tctacaaggt tttcccaaat 1900 agtgcacccc ttgaaggagg gacaaggctg accatatgtg gctgggactt 1950 tggatttcgg aggaataata aatttgattt aaagaaaact agagttctcc 2000 ttggaaatga gagctgcacc ttgactttaa gtgagagcac gatgaataca 2050 ttgaaatgca cagttggtcc tgccatgaat aagcatttca atatgtccat 2100 aatggccacg aattatttca ggacaacaca atacagtaca ttctcctatg 215 0 tggatcctgt aataacaagt atttcgccga aatacggtcc tatggctggt 2200 ggcactttac ttactttaac tggaaattac ctaaacagtg ggaattctag 2250 attggtggaa acacatttca aaacatgtac tttaaaaagt gtgtcaaaca 2300 gtattcttga atgttatacc ccagcccaaa ccatttcaac tgagtttgct 2350 aaattgactt gttaaattga agccaaccga gagacaagca tcttcagtta 2400 ccgtgaagat cccattgtct atgaaattca tcttttatta tccaaccaaa 2450 gtacttggtg gaaagaacct ctcaacattg tcagttttct attttgcttt 2500 gccagtggtg ggagcacaat aacaggtgtt gggaaaaacc tgaattcagt 2550 tagtgtcccg agaatggtca tgaagcagga taaatgtgca aggaacttta 2600 cagtggcatg tcaacatcgc tctaattcag agataatctg ttgtaccact 2650 ccttccctgc aacagctgaa tctgcaactc cccctgaaaa ccaaagcctt 2700 tttcatgtta gatgggatcc tttccaaata ctttgatctc atttatgtac 2750 ataatcctgt gtttaagcct tttgaaaagc cagtgatgat ctcaatgggc 2800 aatgaaaatg tactggaaat taagggaaat gatattgacc ctgaagcagt 2850 taaaggtgaa gtgttaaaag ttggaaataa gagctgtgag aatatacact 2900 agccgtttta tacattctga tgcacggtcc ccaatgacct gctgaaattg 2950 taaatataga aacagcgagc gtggaagcaa gcaatttctt caaccgtcct 3000 atagttcaac tggaaaagta cagatcagaa tttcacagga ttgattgctg 3050 aatatcaaca gtgttgtctc gcactgttat tactacttgg gtttttcctg 3100 agagaaagca tggctgaaaa aattaaagat ctgggcagtg aattagttcg 3150 agagtacaca ctacgatgca ctcctcattt ggataggctt gtaagtgccc 3200 cccaactaca gaagtgtaag gaaatggttt caaatgaatc tgtagactac 3250 cgagctactt ttccagaaga tcagtttcct aattcatctc agaacggttc 3300 atgccgacaa gtgcagtatc ctctgacaga catgtccccc atcctaacta 3350 gtggggactc tgatatatcc agtccattac tgcaaaatac tgtccacatt 3400 gacctcagtg ctctaaatcc agagctggtc caggcagtgc agcatgtagt 3450 gattgggccc agtagcctga ttgtgcattt caatgaagtc ataggaagag 3500 ggcattttgg ttgtgtatat catgggactt tgttggacaa tgatggcaag 3550 aaaattcact gtgctgtgaa atccttgaac agaatcactg acataggaga 3600 agtttcccaa tttctgaccg agggaatcat catgaaagat tttagtcatc 3650 ccaatgtcct ctcgctcctg ggaatctgcc tgcgaagtga agggtctccg 3700 ctggtggtcc taccatacat gaaacatgga gatcttcgaa atttcattcg 3750 cataatccaa aaatgagact ctgtaaaaga tcttattggc tt tggtcttc 3800 aggcatgaaa aagtagccaa gcaaaaagtt tatcttgcaa tgtccacaga 3850 gacttggctg caagaaactg tatgctggat gaaaaattca cagtcaaggt 3900 ggtcttgcca tgctgatttt gagacatgta tgataaagaa tactatagtg 3950 aacaggtgca tacacaacaa aagctgccag tgaagtggat ggctttggaa 4000 agtctgcaaa ctcaaaagtt taccaccaag tcagatgtgt ggtcctttgg 4050 tgggagctga cgtgctcctc tgacaagagg agccccacct tatcctgacg 4100 taaacacctt tgatataact gtttacttgt tgcaagggag aagactccta 4150 actgcccaga caacccgaat ccccttatat gaagtaatgc taaaatgctg 4200 gcaccctaaa gccgaaatgc gcccatcctt ttctgaactg gtgtcccgga 4250 tatcagcgat cttctctact ttcattgggg agcactatgt ccatgtgaac 4300 gctacttatg tgaacgtaaa atgtgtcgct ccgtatcctt ctctgttgtc 4350 atcagaagat aacgctgatg atgaggtgga cacacgacca gcctccttct 4400 gggagacatc atagtgctag tactatgtca aagcaacagt ccacactttg 4450 tccaatggtt ttttcactgc ctgaccttta aaaggccatc gatattcttt 4500 gctcttgcca aaattgcact attataggac ttgtattgtt atttaaatta 4550 ctggattcta aggaatttct tatctgacag agcatcagaa ccagaggctt 4600 ggtcccaca g gccacggacc aatggcctgc ag 4632

<210> 11 <210> 11

<211> 15081 <211> 15081

<212> ADN <212> DNA

<213> Homo sapiens <213> Homo sapiens

<400> 11 <400> 11

ctgcttcact tcacggggcg aacatggcgc acagctgtcg gtggcgcttc 50 ctgcttcact tcacggggcg aacatggcgc acagctgtcg gtggcgcttc 50

cccgcccgac ccgggaccac cgggggcggc ggcggcgggg ggcgccgggg 100 cccgcccgac ccgggaccac cgggggcggc ggcggcgggg ggcgccgggg 100

cctagggggc gccccgcggc aacgcgtccc ggccctgctg cttccccccg 150 cctagggggc gccccgcggc aacgcgtccc ggccctgctg cttccccccg 150

ggcccccggt cggcggtggc ggccccgggg cgcccccctc ccccccggct 200 ggcccccggt cggcggtggc ggccccgggg cgcccccctc ccccccggct 200

gtggcggccg cggcggcggc ggcgggaagc agcggggctg gggttccagg 250 gtggcggccg cggcggcggc ggcgggaagc agcggggctg gggttccagg 250

gggagcggcc gccgcctcag cagcctcctc gtcgtccgcc tcgtcttcgt 300 gggagcggcc gccgcctcag cagcctcctc gtcgtccgcc tcgtcttcgt 300

cttcgtcatc gtcctcagcc tcttcagggc cggccctgct ccgggtgggc 350 cttcgtcatc gtcctcagcc tcttcagggc cggccctgct ccgggtgggc 350

ccgggcttcg acgcggcgct gcaggtctcg gccgccatcg gcaccaacct 400 ccgggcttcg acgcggcgct gcaggtctcg gccgccatcg gcaccaacct 400

gcgccggttc cgggccgtgt ttggggagag cggcggggga ggcggcagcg 450 gcgccggttc cgggccgtgt ttggggagag cggcggggga ggcggcagcg 450

gagagctaac aacacagatc ccatgtagtt ggagaaccaa aggccacata 500 gagagctaac aacacagatc ccatgtagtt ggagaaccaa aggccacata 500

catgacaaaa agactgaacc gttcaggtta cttgcatgga gttggtgctt 550 catgacaaaa agactgaacc gttcaggtta cttgcatgga gttggtgctt 550

aaatgatgag caattcttag gttttggctc agatgaagaa gtcagagtgc 600 aaatgatgag caattcttag gttttggctc agatgaagaa gtcagagtgc 600

gaagtcccac aaggtctcct tcagttaaaa ctagtcctcg aaaacctcgt 650 gaagtcccac aaggtctcct tcagttaaaa ctagtcctcg aaaacctcgt 650

gggagaccta gaagtggctc tgaccgaaat tcagctatcc tctcagatcc 700 gggagaccta gaagtggctc tgaccgaaat tcagctatcc tctcagatcc 700

atctgtgttt tcccctctaa ataaatcaga gaccaaatct ggagataaga 750 atctgtgttt tcccctctaa ataaatcaga gaccaaatct ggagataaga 750

tcaagaagaa agattctaaa agtatagaaa agaagagagg aagacctccc 800 tcaagaagaa agattctaaa agtatagaaa agaagagagg aagacctccc 800

accttccctg gagtaaaaat caaaataaca catggaaagg acatttcaga 850 gttaccaaag ggaaacaaag aagatagcct gaaaaaaatt aaaaggacac 900 cttctgctac gtttcagcaa gccacaaaga ttaaaaaatt aagagcaggt 950 aaactctctc ctctcaagtc taagtttaag acagggaagc ttcaaatagg 1000 aaggaagggg gtacaaattg tacgacggag aggaaggcct ccatcaacag 1050 aaaggataaa gaccccttcg ggtctcctca ttaattctga actggaaaag 1100 ccccagaaag tccggaaaga caaggaagga acacctccac ttacaaaaga 1150 agataagaca gttgtcagac aaagccctcg aaggattaag ccagttagga 1200 ttattccttc ttcaaaaagg acagatgcaa ccattgctaa gcaactctta 1250 cagagggcaa aaaagggggc tcaaaagaaa attgaaaaag aagcagctca 1300 gctgcaggga agaaaggtga agacacaggt caaaaatatt cgacagttca 1350 tcatgcctgt tgtcagtgct atctcctcgc ggatcattaa gacccctcgg 1400 cggtttatag aggatgagga ttatgaccct ccaattaaaa ttgcccgatt 1450 agagtctaca ccgaatagta gattcagtgc cccgtcctgt ggatcttctg 1500 aaaaatcaag tgcagcttct cagcactcct ctcaaatgtc ttcagactcc 1550 tctcgatcta gtagccccag tgttgatacc tccacagact ctcaggcttc 1600 tgaggagatt caggtacttc ctgaggagcg gagcgatacc cctgaagttc 1650 atcctccact gcccatttcc cagtccccag aaaatgagag taatgatagg 1700 agaagcagaa ggtattcagt gtcggagaga agttttggat ctagaacgac 1750 gaaaaaatta tcaactctac aaagtgcccc ccagcagcag acctcctcgt 1800 ctccacctcc acctctgctg actccaccgc caccactgca gccagcctcc 1850 agtatctctg accacacacc ttggcttatg cctccaacaa tccccttagc 1900 atcaccattt ttgcctgctt ccactgctcc tatgcaaggg aagcgaaaat 1950 ctattttgcg agaaccgaca tttaggtgga cttctttaaa gcattctagg 2000 tcagagccac aatacttttc ctcagcaaag tatgccaaag aaggtcttat 2050 tcgcaaacca atatttgata atttccgacc ccctccacta actcccgagg 2100 acgttggctt tgcatctggt ttttctgcat ctggtaccgc tgcttcagcc 2150 cgattgtttt cgccactcca ttctggaaca aggtttgata tgcacaaaag 2200 gagccctctt ctgagagctc caagatttac tccaagtgag gctcactcta 2250 gaatatttga gtctgtaacc ttgcctagta atcgaacttc tgctggaaca 2300 tcttcttcag gagtatccaa tagaaaaagg aaaagaaaag tgtttagtcc 2350 tattcgatct gaaccaagat ctccttctca ctccatgagg acaagaagtg 2400 gaaggcttag tagttctgag ctctcacctc tcaccccccc gtcttctgtc 2450 tcttcctcgt taagcatttc tgttagtcct cttgccacta gtgccttaaa 2500 cccaactttt acttttcctt ctcattccct gactcagtct ggggaatctg 2550 cagagaaaaa tcagagacca aggaagcaga ctagtgctcc ggcagagcca 2600 ttttcatcaa gtagtcctac tcctctcttc ccttggttta ccccaggctc 2650 tcagactgaa agagggagaa ataaagacaa ggcccccgag gagctgtcca 2700 aagatcgaga tgctgacaag agcgtggaga aggacaagag tagagagaga 2750 gaccgggaga gagaaaagga gaataagcgg gagtcaagga aagagaaaag 2800 gaaaaaggga tcagaaattc agagtagttc tgctttgtat cctgtgggta 2850 gggtttccaa agagaaggtt gttggtgaag atgttgccac ttcatcttct 2900 gccaaaaaag caacagggcg gaagaagtct tcatcacatg attctgggac 2950 tgatattact tctgtgactc ttggggatac aacagctgtc aaaaccaaaa 3000 tacttataaa gaaagggaga ggaaatctgg aaaaaaccaa cttggacctc 3050 ggcccaactg ccccatccct ggagaaggag aaaaccctct gcctttccac 3100 tccttcatct agcactgtta aacattccac ttcctccata ggctccatgt 3150 tggctcaggc agacaagctt ccaatgactg acaagagggt tgccagcctc 3200 ctaaaaaagg ccaaagctca gctctgcaag attgagaaga gtaagagtct 3250 taaacaaacc gaccagccca aagcacaggg tcaagaaagt gactcatcag 3300 agacctctgt gcgaggaccc cggattaaac atgtctgcag aagagcagct 3350 gttgcccttg gccgaaaacg agctgtgttt cctgatgaca tgcccaccct 3400 gagtgcctta ccatgggaag aacgagaaaa gattttgtct tccatgggga 3450 atgatgacaa gtcatcaatt gctggctcag aagatgctga acctcttgct 3500 ccacccatca aaccaattaa acctgtcact agaaacaagg caccccagga 3550 acctccagta aagaaaggac gtcgatcgag gcggtgtggg cagtgtcccg 3600 gctgccaggt gcctgaggac tgtggtgttt gtactaattg cttagataag 3650 cccaagtttg gtggtcgcaa tataaagaag cagtgctgca agatgagaaa 3700 atgtcagaat ctacaatgga tgccttccaa agcctacctg cagaagcaag 3750 ctaaagctgt gaaaaagaaa gagaaaaagt ctaagaccag tgaaaagaaa 3800 gacagcaaag agagcagtgt tgtgaagaac gtggtggact ctagtcagaa 3850 acctacccca tcagcaagag aggatcctgc cccaaagaaa agcagtagtg 3900 agcctcctcc acgaaagccc gtcgaggaaa agagtgaaga agggaatgtc 3950 tcggcccctg ggcctgaatc caaacaggcc accactccag cttccaggaa 4000 gtcaagcaag caggtctccc agccagcact ggtcatcccg cctcagccac 4050 ctactacagg accgccaaga aaagaagttc ccaaaaccac tcctagtgag 4100 cccaagaaaa agcagcctcc accaccagaa tcaggtccag agcagagcaa 4150 acagaaaaaa gtggctcccc gcccaagtat ccctgtaaaa caaaaaccaa 4200 aagaaaagga aaaaccacct ccggtcaata agcaggagaa tgcaggcact 4250 ttgaacatcc tcagcactct ctccaatggc aatagttcta agcaaaaaat 4300 tccagcagat ggagtccaca ggatcagagt ggactttaag gaggattgtg 4350 aagcagaaaa tgtgtgggag atgggaggct taggaatctt gacttctgtt 4400 cctataacac ccagggtggt ttgctttctc tgtgccagta gtgggcatgt 4450 agagtttgtg tattgccaag tctgttgtga gcccttccac aagttttgtt 4500 tagaggagaa cgagcgccct ctggaggacc agctggaaaa ttggtgttgt 4550 cgtcgttgca aattctgtca cgtttgtgga aggcaacatc aggctacaaa 4600 gcagctgctg gagtgtaata agtgccgaaa cagctatcac cctgagtgcc 4650 tgggaccaaa ctaccccacc aaacccacaa agaagaagaa agtctggatc 4700 tgtaccaagt gtgttcgctg taagagctgt ggatccacaa ctccaggcaa 4750 agggtgggat gcacagtggt ctcatgattt ctcactgtgt catgattgcg 4800 ccaagctctt tgctaaagga aacttctgcc ctctctgtga caaatgttat 4850 gatgatgatg actatgagag taagatgatg caatgtggaa agtgtgatcg 4900 ctgggtccat tccaaatgtg agaatctttc agatgagatg tatgagattc 4950 tatctaatct gccagaaagt gtggcctaca cttgtgtgaa ctgtactgag 5000 cggcaccctg cagagtggcg actggccctt gaaaaagagc tgcagatttc 5050 tctgaagcaa gttctgacag ctttgttgaa ttctcggact accagccatt 5100 tgctacgcta ccggcaggct gccaagcctc cagacttaaa tcccgagaca 5150 gaggagagta taccttcccg cagctccccc gaaggacctg atccaccagt 5200 tcttactgag gtcagcaaac aggatgatca gcagccttta gatctagaag 5250 gagtcaagag gaagatggac caagggaatt acacatctgt gttggagttc 5300 agtgatgata ttgtgaagat cattcaagca gccattaatt cagatggagg 5350 acagccagaa attaaaaaag ccaacagcat ggtcaagtcc ttcttcattc 5400 ggcaaatgga acgtgttttt ccatggttca gtgtcaaaaa gtccaggttt 5450 tgggagccaa ataaagtatc aagcaacagt gggatgttac caaacgcagt 5500 gcttccacct tcacttgacc ataattatgc tcagtggcag gagcgagagg 5550 aaaacagcca cactgagcag cctcctttaa tgaagaaaat cattccagct 5600 cccaaaccca aaggtcctgg agaaccagac tcaccaactc ctctgcatcc 5650 tcctacacca ccaattttga gtactgatag gagtcgagaa gacagtccag 5700 agctgaaccc acccccaggc atagaagaca atagacagtg tgcgttatgt 5750 ttgacttatg gtgatgacag tgctaatgat gctggtcgtt tactatatat 5800 tggccaaaat gagtggacac atgtaaattg tgctttgtgg tcagcggaag 5850 tgtttgaaga tgatgacgga tcactaaaga atgtgcatat ggctgtgatc 5900 aggggcaagc agctgagatg tgaattctgc caaaagccag gagccaccgt 5950 gggttgctgt ctcacatcct gcaccagcaa ctatcacttc atgtgttccc 6000 gagccaagaa ctgtgtcttt ctggatgata aaaaagtata ttgccaacga 6050 catcgggatt tgatcaaagg cgaagtggtt cctgagaatg gatttgaagt 6100 tttcagaaga gtgtttgtgg actttgaagg aatcagcttg agaaggaagt 6150 ttctcaatgg cttggaacca gaaaatatcc acatgatgat tgggtctatg 6200 acaatcgact gcttaggaat tctaaatgat ctctccgact gtgaagataa 6250 gctctttcct attggatatc agtgttccag ggtatactgg agcaccacag 6300 atgctcgcaa gcgctgtgta tatacatgca agatagtgga gtgccgtcct 6350 ccagtcgtag agccggatat caacagcact gttgaacatg atgaaaacag 6400 gaccattgcc catagtccaa catcttttac agaaagttca tcaaaagaga 6450 gtcaaaacac agctgaaatt ataagtcctc catcaccaga ccgacctcct 6500 cattcacaaa cctctggctc ctgttattat catgtcatct caaaggtccc 6550 caggattcga acacccagtt attctccaac acagagatcc cctggctgtc 6600 gaccgttgcc ttctgcagga agtcctaccc caaccactca tgaaatagtc 6650 acagtaggtg atcctttact ctcctctgga cttcgaagca ttggctccag 6700 gcgtcacagt acctcttcct tatcacccca gcggtccaaa ctccggataa 6750 tgtctccaat gagaactggg aatacttact ctaggaataa tgtttcctca 6800 gtctccacca ccgggaccgc tactgatctt gaatcaagtg ccaaagtagt 6850 tgatcatgtc ttagggccac tgaattcaag tactagttta gggcaaaaca 6900 cttccacctc ttcaaatttg caaaggacag tggttactgt aggcaataaa 6950 aacagtcact tggatggatc ttcatcttca gaaatgaagc agtccagtgc 7000 ttcagacttg gtgtccaaga gctcctcttt aaagggagag aagaccaaag 7050 tgctgagttc caagagctca gagggatctg cacataatgt ggcttaccct 7100 ggaattccta aactggcccc acaggttcat aacacaacat ctagagaact 7150 gaatgttagt aaaatcggct cctttgctga accctcttca gtgtcgtttt 7200 cttctaaaga ggccctctcc ttcccacacc tccatttgag agggcaaagg 7250 aatgatcgag accaacacac agattctacc caatcagcaa actcctctcc 7300 agatgaagat actgaagtca aaaccttgaa gctatctgga atgagcaaca 7350 gatcatccat tatcaacgaa catatgggat ctagttccag agataggaga 7400 cagaaaggga aaaaatcctg taaagaaact ttcaaagaaa agcattccag 7450 taaatctttt ttggaacctg gtcaggtgac aactggtgag gaaggaaact 7500 tgaagccaga gtttatggat gaggttttga ctcctgagta tatgggccaa 7550 cgaccatgta acaatgtttc ttctgataag attggtgata aaggcctttc 7600 tatgccagga gtccccaaag ctccacccat gcaagtagaa ggatctgcca 7650 aggaattaca ggcaccacgg aaacgcacag tcaaagtgac actgacacct 7700 ctaaaaatgg aaaatgagag tcaatccaaa aatgccctga aagaaagtag 7750 tcctgcttcc cctttgcaaa tagagtcaac atctcccaca gaaccaattt 7800 cagcctctga aaatccagga gatggtccag tggcccaacc aagccccaat 7850 aatacctcat gccaggattc tcaaagtaac aactatcaga atcttccagt 7900 acaggacaga aacctaatgc ttccagatgg ccccaaacct caggaggatg 7950 gctcttttaa aaggaggtat ccccgtcgca gtgcccgtgc acgttctaac 8000 atgttttttg ggcttacccc actctatgga gtaagatcct atggtgaaga 8050 agacattcca ttctacagca gctcaactgg gaagaagcga ggcaagagat 8100 cagctgaagg acaggtggat ggggccgatg acttaagcac ttcagatgaa 8150 gacgacttat actattacaa cttcactaga acagtgattt cttcaggtgg 8200 agaggaacga ctggcatccc ataatttatt tcgggaggag gaacagtgtg 8250 atcttccaaa aatctcacag ttggatggtg ttgatgatgg gacagagagt 8300 gatactagtg tcacagccac aacaaggaaa agcagccaga ttccaaaaag 8350 aaatggtaaa gaaaatggaa cagagaactt aaagattgat agacctgaag 8400 atgctgggga gaaagaacat gtcactaaga gttctgttgg ccacaaaaat 8450 gagccaaaga tggataactg ccattctgta agcagagtta aaacacaggg 8500 acaagattcc ttggaagctc agctcagctc attggagtca agccgcagag 8550 tccacacaag taccccctcc gacaaaaatt tactggacac ctataatact 8600 gagctcctga aatcagattc agacaataac aacagtgatg actgtgggaa 8650 tatcctgcct tcagacatta tggactttgt actaaagaat actccatcca 8700 tgcaggcttt gggtgagagc ccagagtcat cttcatcaga actcctgaat 8750 cttggtgaag gattgggtct tgacagtaat cgtgaaaaag acatgggtct 8800 ttttgaagta ttttctcagc agctgcctac aacagaacct gtggatagta 8850 gtgtctcttc ctctatctca gcagaggaac agtttgagtt gcctctagag 8900 ctaccatctg atctgtctgt cttgaccacc cggagtccca ctgtccccag 8950 ccagaatccc agtagactag ctgttatctc agactcaggg gagaagagag 9000 taaccatcac agaaaaatct gtagcctcct ctgaaagtga cccagcactg 9050 ctgagcccag gagtagatcc aactcctgaa ggccacatga ctcctgatca 9100 ttttatccaa ggacacatgg atgcagacca catctctagc cctccttgtg 9150 gttcagtaga gcaaggtcat ggcaacaatc aggatttaac taggaacagt 9200 agcacccctg gccttcaggt acctgtttcc ccaactgttc ccatccagaa 9250 ccagaagtat gtgcccaatt ctactgatag tcctggcccg tctcagattt 9300 ccaatgcagc tgtccagacc actccacccc acctgaagcc agccactgag 9350 aaactcatag ttgttaacca gaacatgcag ccactttatg ttctccaaac 9400 tcttccaaat ggagtgaccc aaaaaatcca attgacctct tctgttagtt 9450 ctacacccag tgtgatggag acaaatactt cagtattggg acccatggga 9500 ggtggtctca cccttaccac aggactaaat ccaagcttgc caacttctca 9550 atctttgttc ccttctgcta gcaaaggatt gctacccatg tctcatcacc 9600 agcacttaca ttccttccct gcagctactc aaagtagttt cccaccaaac 9650 atcagcaatc ctccttcagg cctgcttatt ggggttcagc ctcctccgga 9700 tccccaactt ttggtttcag aatccagcca gaggacagac ctcagtacca 9750 cagtagccac tccatcctct ggactcaaga aaagacccat atctcgtcta 9800 cagacccgaa agaataaaaa acttgctccc tctagtaccc cttcaaacat 9850 tgccccttct gatgtggttt ctaatatgac attgattaac ttcacaccct 9900 cccagcttcc taatcatcca agtctgttag atttggggtc acttaatact 9950 tcatctcacc gaactgtccc caacatcata aaaagatcta aatctagcat 10000 catgtatttt gaaccggcac ccctgttacc acagagtgtg ggaggaactg 10050 ctgccacagc ggcaggcaca tcaacaataa gccaggatac tagccacctc 10100 acatcagggt ctgtgtctgg cttggcatcc agttcctctg tcttgaatgt 10150 tgtatccatg caaactacca caacccctac aagtagtgcg tcagttccag 10200 gacacgtcac cttaaccaac ccaaggttgc ttggtacccc agatattggc 10250 tcaataagca atcttttaat caaagctagc cagcagagcc tggggattca 10300 ggaccagcct gtggctttac cgccaagttc aggaatgttt ccacaactgg 10350 ggacatcaca gaccccctct actgctgcaa taacagcggc atctagcatc 10400 tgtgtgctcc cctccactca gactacgggc ataacagccg cttcaccttc 10450 tggggaagca gacgaacact atcagcttca gcatgtgaac cagctccttg 10500 ccagcaaaac tgggattcat tcttcccagc gtgatcttga ttctgcttca 10550 gggccccagg tatccaactt tacccagacg gtagacgctc ctaatagcat 10600 gggactggag cagaacaagg ctttatcctc agctgtgcaa gccagcccca 10650 cctctcctgg gggttctcca tcctctccat cttctggaca gcggtcagca 10700 agcccttcag tgccgggtcc cactaaaccc aaaccaaaaa ccaaacggtt 10750 tcagctgcct ctagacaaag ggaatggcaa gaagcacaaa gtttcccatt 10800 tgcggaccag ttcttctgaa gcacacattc cagaccaaga aacgacatcc 10850 ctgacctcag gcacagggac tccaggagca gaggctgagc agcaggatac 10900 agctagcgtg gagcagtcct cccagaagga gtgtgggcaa cctgcagggc 10950 aagtcgctgt tcttccggaa gttcaggtga cccaaaatcc agcaaatgaa 11000 caagaaagtg cagaacctaa aacagtggaa gaagaggaaa gtaatttcag 11050 ctccccactg atgctttggc ttcagcaaga acaaaagcgg aaggaaagca 11100 ttactgagaa aaaacccaag aaaggacttg tttttgaaat ttccagtgat 11150 gatggctttc agatctgtgc agaaagtatt gaagatgcct ggaagtcatt 11200 gacagataaa gtccaggaag ctcgatcaaa tgcccgccta aagcagctct 11250 catttgcagg tgttaacggt ttgaggatgc tggggattct ccatgatgca 11300 gttgtgttcc tcattgagca gctgtctggt gccaagcact gtcgaaatta 11350 caaattccgt ttccacaagc cagaggaggc caatgaaccc cccttgaacc 11400 ctcacggctc agccagggct gaagtccacc tcaggaagtc agcatttgac 11450 atgtttaact tcctggcttc taaacatcgt cagcctcctg aatacaaccc 11500 caatgatgaa gaagaggagg aggtacagct gaagtcagct cggagggcaa 11550 ctagcatgga tctgccaatg cccatgcgct tccggcactt aaaaaagact 11600 tctaaggagg cagttggtgt ctacaggtct cccatccatg gccggggtct 11650 tttctgtaag agaaacattg atgcaggtga gatggtgatt gagtatgccg 11700 gcaacgtcat ccgctccatc cagactgaca agcgggaaaa gtattacgac 11750 agcaagggca ttggttgcta tatgttccga attgatgact cagaggtagt 11800 ggatgccacc atgcatggaa atgctgcacg cttcatcaat cactcgtgtg 11850 agcctaactg ctattctcgg gtcatcaata ttgatgggca gaagcacatt 11900 gtcatctttg ccatgcgtaa gatctaccga ggagaggaac tcacttacga 11950 ctataagttc cccattgagg atgccagcaa caagctgccc tgcaactgtg 12000 gcgccaagaa atgccggaag ttcctaaact aaagctgctc ttctccccca 12050 gtgttggagt gcaaggaggc ggggccatcc aaagcaacgc tgaaggcctt 12100 ttccagcagc tgggagctcc cggattgcgt ggcacagctg aggggcctct 12150 gtgatggctg agctctctta tgtcctatac tcacatcaga catgtgatca 12200 tagtcccaga gacagagttg aggtctcgaa gaaaagatcc atgatcggct 12250 ttctcctggg gcccctccaa ttgtttactg ttagaaagtg ggaatggggt 12300 ccctagcaga cttgcctgga aggagcctat tatagagggt tggttatgtt 12350 gggagattgg gcctgaattt ctccacagaa ataagttgcc atcctcaggt 12400 tggccctttc ccaagcactg taagtgagtg ggtcaggcaa agccccaaat 12450 ggagggttgg ttagattcct gacagtttgc cagccaggcc ccacctacag 12500 cgtctgtcga acaaacagag gtctggtggt tttccctact atcctcccac 12550 tcgagagttc acttctggtt gggagacagg attcctagca cctccggtgt 12600 caaaaggctg tcatggggtt gtgccaatta attaccaaac attgagcctg 12650 caggctttga gtgggagtgt tgcccccagg agccttatct cagccaatta 12700 cctttcttga cagtaggagc ggcttccctc tcccattccc tcttcactcc 12750 cttttcttcc tttcccctgt cttcatgcca ctgctttccc atgcttcttt 12800 cgggttgtag gggagactga ctgcctgctc aaggacactc cctgctgggc 12850 ataggatgtg cctgcaaaaa gttccctgag cctgtaagca ctccaggtgg 12900 ggaagtggac aggagccatt ggtcataacc agacagaatt tggaaacatt 12950 ttcataaagc tccatggaga gttttaaaga aacatatgta gcatgatttt 13000 gtaggagagg aaaaagatta tttaaatagg atttaaatca tgcaacaacg 13050 agagtatcac agccaggatg acccttgggt cccattccta agacatggtt 13100 actttatttt ccccttgtta agacatagga agacttaatt tttaaacggt 13150 cagtgtccag ttgaaggcag aacactaatc agatttcaag gcccacaact 13200 tggggactag accaccttat gttgagggaa ctctgccacc tgcgtgcaac 13250 ccacagctaa agtaaattca atgacactac tgccctgatt actccttagg 13300 atgtggtcaa aacagcatca aatgtttctt ctcttccttt ccccaagaca 13350 gagtcctgaa cctgttaaat taagtcattg gattttactc tgttctgttt 13400 acagtttact atttaaggtt ttataaatgt aaatatattt tgtatatttt 13450 tctatgagaa gcacttcata gggagaagca cttatgacaa ggctattttt 13500 taaaccgcgg tattatccta atttaaaaga agatcggttt ttaataattt 13550 tttattttca taggatgaag ttagagaaaa tattcagctg tacacacaaa 13600 gtctggtttt tcctgcccaa cttccccctg gaaggtgtac tttttgttgt 13650 ttaatgtgta gcttgtttgt gccctgttga cataaatgtt tcctgggttt 13700 gctctttgac aataaatgga gaaggaaggt cacccaactc cattgggcca 13750 ctcccctcct tcccctattg aagctcctca aaaggctaca gtaatatctt 13800 gatacaacag attctcttct ttcccgcctc tctcctttcc ggcgcaactt 13850 ccagagtggt gggagacggc aatctttaca tttccctcat ctttcttact 13900 tcagagttag caaacaacaa gttgaatggc aacttgacat ttttgcatca 13950 ccatctgcct cataggccac tctttccttt ccctctgccc accaagtcct 14000 catatctgca gagaacccat tgatcacctt gtgccctctt ttggggcagc 14050 ctgttgaaac tgaagcacag tctgaccact cacgataaag cagatttttc 14100 tctgcctctg ccacaaggtt tcagagtagt gtagtccaag tagagggtgg 14150 ggcacccttt tctcgccgca agaagcccat tcctatggaa gtctagcaaa 14200 gcaatacgac tcagcccagc actctctgcc ccaggactca tggctctgct 14250 gtgccttcca tcctgggctc ccttctctcc tgtgacctta agaactttgt 14300 ctggtggctt tgctggaaca ttgtcactgt tttcactgtc atgcagggag 14350 cccagcactg tggccaggat ggcagagact tccttgtcat catggagaag 14400 tgccagcagg ggactgggaa aagcactcta cccagacctc acctcccttc 14450 ctccttttgc ccatgaacaa gatgcagtgg ccctaggggt tccactagtg 14500 tctgctttcc tttattattg cactgtgtga ggtttttttg taaatccttg 14550 tattcctatt ttttttaaag aaaaaaaaaa aaccttaagc tgcatttgtt 14600 actgaaatga ttaatgcact gatgggtcct gaattcacct tgagaaagac 14650 ccaaaggcca gtcagggggt ggggggaact cagctaaata gacctagtta 14700 ctgccctgct aggccatgct gtactgtgag cccctcctca ctctctacca 14750 accctaaacc ctgaggacag gggaggaacc cacagcttcc ttctcctgcc 14800 agctgcagat ggtttgcctt gcctttccac cccctaattg tcaaccacaa 14850 aaatgagaaa ttcctcttct agctcagcct tgagtccatt gccaaatttt 14900 cagcacacct gccagcaact tgggggaata agcgaaggtt tccctacaag 14950 agggaaagaa ggcaaaaacg gcacagctat ctccaaacac atctgagttc 15000 atttcaaaag tgaccaaggg aatctccgca caaaagtgca gattgaggaa 15050 ttgtgatggg tcattcccaa gaatccccca a 15081 accttccctg gagtaaaaat caaaataaca catggaaagg acatttcaga 850 gttaccaaag ggaaacaaag aagatagcct gaaaaaaatt aaaaggacac 900 gtttcagcaa cttctgctac gccacaaaga ttaaaaaatt aagagcaggt 950 aaactctctc ctctcaagtc taagtttaag acagggaagc ttcaaatagg 1000 aaggaagggg gtacaaattg tacgacggag aggaaggcct ccatcaacag 1050 gaccccttcg aaaggataaa ggtctcctca ttaattctga actggaaaag 1100 tccggaaaga ccccagaaag caaggaagga acacctccac ttacaaaaga 1150 agataagaca gttgtcagac aaagccctcg aaggattaag ccagttagga 1200 ttattccttc ttcaaaaagg acagatgcaa gcaactctta ccattgctaa 1250 cagagggcaa aaaagggggc tcaaaagaaa attgaaaaag aagcagctca 1300 agaaaggtga gctgcaggga agacacaggt caaaaatatt cgacagttca 1350 tcatgcctgt tgtcagtgct atctcctcgc ggatcattaa gacccctcgg 1400 cggtttatag aggatgagga ttatgaccct ccaattaaaa ttgcccgatt 1450 ccgaatagta agagtctaca gattcagtgc cccgtcctgt ggatcttctg 1500 aaaaatcaag tgcagcttct cagcactcct ctcaaatgtc ttcagactcc 1550 tctcgatcta gtagccccag tgttgatacc tccacagact ctcaggcttc 1600 tgaggagatt caggtacttc ctgag gagcg gagcgatacc cctgaagttc 1650 atcctccact gcccatttcc cagtccccag aaaatgagag taatgatagg 1700 agaagcagaa ggtattcagt gtcggagaga agttttggat ctagaacgac 1750 gaaaaaatta tcaactctac aaagtgcccc ccagcagcag acctcctcgt 1800 ctccacctcc acctctgctg actccaccgc caccactgca gccagcctcc 1850 agtatctctg accacacacc ttggcttatg cctccaacaa tccccttagc 1900 atcaccattt ttgcctgctt ccactgctcc tatgcaaggg aagcgaaaat 1950 agaaccgaca ctattttgcg cttctttaaa tttaggtgga gcattctagg 2000 tcagagccac aatacttttc ctcagcaaag tatgccaaag aaggtcttat 2050 atatttgata tcgcaaacca atttccgacc ccctccacta actcccgagg 2100 acgttggctt tgcatctggt ttttctgcat ctggtaccgc tgcttcagcc 2150 cgattgtttt cgccactcca ttctggaaca aggtttgata tgcacaaaag 2200 gagccctctt ctgagagctc caagatttac tccaagtgag gctcactcta 2250 gaatatttga gtctgtaacc ttgcctagta atcgaacttc tgctggaaca 2300 tcttcttcag gagtatccaa tagaaaaagg aaaagaaaag tgtttagtcc 2350 tattcgatct gaaccaagat ctccttctca ctccatgagg acaagaagtg 2400 gaaggcttag tagttctgag ctctcacctc tcaccccccc gtcttct gtc 2450 tcttcctcgt taagcatttc tgttagtcct gtgccttaaa cttgccacta 2500 cccaactttt acttttcctt ctcattccct gactcagtct ggggaatctg 2550 tcagagacca cagagaaaaa aggaagcaga ctagtgctcc ggcagagcca 2600 ttttcatcaa gtagtcctac tcctctcttc ccttggttta ccccaggctc 2650 agagggagaa tcagactgaa ataaagacaa gagctgtcca ggcccccgag 2700 aagatcgaga tgctgacaag agcgtggaga aggacaagag tagagagaga 2750 gagaaaagga gaccgggaga gaataagcgg gagtcaagga aagagaaaag 2800 gaaaaaggga tcagaaattc agagtagttc tgctttgtat cctgtgggta 2850 gggtttccaa agagaaggtt gttggtgaag atgttgccac ttcatcttct 2900 gccaaaaaag caacagggcg gaagaagtct tcatcacatg attctgggac 2950 tgatattact tctgtgactc ttggggatac aacagctgtc aaaaccaaaa 3000 gaaagggaga tacttataaa ggaaatctgg aaaaaaccaa cttggacctc 3050 ggcccaactg ccccatccct ggagaaggag aaaaccctct gcctttccac 3100 tccttcatct agcactgtta aacattccac ttcctccata ggctccatgt 3150 tggctcaggc agacaagctt ccaatgactg acaagagggt tgccagcctc 3200 ctaaaaaagg ccaaagctca gctctgcaag attgagaaga gtaagagtct 3250 taaacaaacc GACC agccca aagcacaggg tcaagaaagt gactcatcag 3300 agacctctgt gcgaggaccc cggattaaac atgtctgcag aagagcagct 3350 gttgcccttg gccgaaaacg agctgtgttt cctgatgaca tgcccaccct 3400 gagtgcctta ccatgggaag aacgagaaaa gattttgtct tccatgggga 3450 atgatgacaa gtcatcaatt gctggctcag aagatgctga acctcttgct 3500 aaccaattaa ccacccatca acctgtcact agaaacaagg caccccagga 3550 acctccagta aagaaaggac gtcgatcgag gcggtgtggg cagtgtcccg 3600 gctgccaggt gcctgaggac tgtggtgttt gtactaattg cttagataag 3650 cccaagtttg gtggtcgcaa tataaagaag cagtgctgca agatgagaaa 3700 atgtcagaat ctacaatgga tgccttccaa agcctacctg cagaagcaag 3750 ctaaagctgt gaaaaagaaa gagaaaaagt ctaagaccag tgaaaagaaa 3800 gacagcaaag agagcagtgt tgtgaagaac gtggtggact ctagtcagaa 3850 acctacccca tcagcaagag aggatcctgc cccaaagaaa agcagtagtg 3900 agcctcctcc acgaaagccc gtcgaggaaa agagtgaaga agggaatgtc 3950 tcggcccctg ggcctgaatc caaacaggcc accactccag cttccaggaa 4000 gtcaagcaag caggtctccc agccagcact ggtcatcccg cctcagccac 4050 ctactacagg accgccaaga aaagaagttc ccaaaac cac tcctagtgag 4100 cccaagaaaa agcagcctcc accaccagaa tcaggtccag agcagagcaa 4150 acagaaaaaa gtggctcccc gcccaagtat ccctgtaaaa caaaaaccaa 4200 aaaaccacct aagaaaagga ccggtcaata agcaggagaa tgcaggcact 4250 ttgaacatcc tcagcactct ctccaatggc aatagttcta agcaaaaaat 4300 tccagcagat ggagtccaca ggatcagagt ggactttaag gaggattgtg 4350 aagcagaaaa tgtgtgggag atgggaggct taggaatctt gacttctgtt 4400 cctataacac ccagggtggt ttgctttctc tgtgccagta gtgggcatgt 4450 agagtttgtg tattgccaag tctgttgtga gcccttccac aagttttgtt 4500 tagaggagaa cgagcgccct ctggaggacc agctggaaaa ttggtgttgt 4550 aattctgtca cgtcgttgca cgtttgtgga aggcaacatc aggctacaaa 4600 gcagctgctg gagtgtaata agtgccgaaa cagctatcac cctgagtgcc 4650 tgggaccaaa ctaccccacc aaacccacaa agaagaagaa agtctggatc 4700 tgtaccaagt gtgttcgctg taagagctgt ggatccacaa ctccaggcaa 4750 agggtgggat gcacagtggt ctcatgattt ctcactgtgt catgattgcg 4800 tgctaaagga ccaagctctt aacttctgcc ctctctgtga caaatgttat 4850 gatgatgatg actatgagag taagatgatg caatgtggaa agtgtgatcg 4900 ctg ggtccat tccaaatgtg agaatctttc agatgagatg tatgagattc 4950 tatctaatct gccagaaagt gtggcctaca cttgtgtgaa ctgtactgag 5000 cggcaccctg cagagtggcg actggccctt gaaaaagagc tgcagatttc 5050 tctgaagcaa gttctgacag ctttgttgaa ttctcggact accagccatt 5100 tgctacgcta ccggcaggct gccaagcctc tcccgagaca cagacttaaa 5150 gaggagagta taccttcccg cagctccccc gaaggacctg atccaccagt 5200 tcttactgag gtcagcaaac aggatgatca gcagccttta gatctagaag 5250 gagtcaagag gaagatggac caagggaatt acacatctgt gttggagttc 5300 agtgatgata ttgtgaagat cattcaagca gccattaatt cagatggagg 5350 acagccagaa attaaaaaag ccaacagcat ggtcaagtcc ttcttcattc 5400 acgtgttttt ggcaaatgga gtgtcaaaaa ccatggttca gtccaggttt 5450 tgggagccaa ataaagtatc aagcaacagt gggatgttac caaacgcagt 5500 gcttccacct tcacttgacc ataattatgc tcagtggcag gagcgagagg 5550 aaaacagcca cactgagcag cctcctttaa tgaagaaaat cattccagct 5600 cccaaaccca aaggtcctgg agaaccagac tcaccaactc ctctgcatcc 5650 ccaattttga tcctacacca gtactgatag gagtcgagaa gacagtccag 5700 agctgaaccc acccccaggc Ataga AGACA atagacagtg tgcgttatgt 5750 ttgacttatg gtgatgacag tgctaatgat gctggtcgtt tactatatat 5800 tggccaaaat gagtggacac atgtaaattg tgctttgtgg tcagcggaag 5850 tgatgacgga tgtttgaaga tcactaaaga atgtgcatat ggctgtgatc 5900 aggggcaagc agctgagatg tgaattctgc caaaagccag gagccaccgt 5950 gggttgctgt ctcacatcct gcaccagcaa ctatcacttc atgtgttccc 6000 ctgtgtcttt gagccaagaa aaaaagtata ctggatgata ttgccaacga 6050 catcgggatt tgatcaaagg cgaagtggtt cctgagaatg gatttgaagt 6100 tttcagaaga gtgtttgtgg actttgaagg aatcagcttg agaaggaagt 6150 ttctcaatgg cttggaacca gaaaatatcc acatgatgat tgggtctatg 6200 acaatcgact gcttaggaat tctaaatgat ctctccgact gtgaagataa 6250 gctctttcct attggatatc agtgttccag ggtatactgg agcaccacag 6300 gcgctgtgta atgctcgcaa agatagtgga tatacatgca gtgccgtcct 6350 ccagtcgtag agccggatat caacagcact gttgaacatg atgaaaacag 6400 catagtccaa gaccattgcc agaaagttca catcttttac tcaaaagaga 6450 gtcaaaacac agctgaaatt ataagtcctc catcaccaga ccgacctcct 6500 cattcacaaa cctctggctc ctgttattat catgtcatct caaaggt ccc 6550 caggattcga acacccagtt attctccaac acagagatcc cctggctgtc 6600 ttctgcagga gaccgttgcc agtcctaccc caaccactca tgaaatagtc 6650 atcctttact acagtaggtg cttcgaagca ctcctctgga ttggctccag 6700 gcgtcacagt acctcttcct tatcacccca gcggtccaaa ctccggataa 6750 tgtctccaat gagaactggg aatacttact tgtttcctca ctaggaataa 6800 gtctccacca ccgggaccgc tactgatctt gaatcaagtg ccaaagtagt 6850 tgatcatgtc ttagggccac tgaattcaag tactagttta gggcaaaaca 6900 cttccacctc ttcaaatttg caaaggacag tggttactgt aggcaataaa 6950 aacagtcact tggatggatc ttcatcttca gaaatgaagc agtccagtgc 7000 ttcagacttg gtgtccaaga gctcctcttt aaagggagag aagaccaaag 7050 caagagctca tgctgagttc gagggatctg cacataatgt ggcttaccct 7100 ggaattccta aactggcccc acaggttcat aacacaacat ctagagaact 7150 aaaatcggct gaatgttagt cctttgctga accctcttca gtgtcgtttt 7200 cttctaaaga ggccctctcc ttcccacacc tccatttgag agggcaaagg 7250 aatgatcgag accaacacac agattctacc caatcagcaa actcctctcc 7300 agatgaagat actgaagtca aaaccttgaa atgagcaaca gctatctgga 7350 gatcatccat tat caacgaa catatgggat ctagttccag agataggaga 7400 cagaaaggga aaaaatcctg taaagaaact ttcaaagaaa agcattccag 7450 taaatctttt ttggaacctg gtcaggtgac aactggtgag gaaggaaact 7500 gtttatggat tgaagccaga ctcctgagta gaggttttga tatgggccaa 7550 cgaccatgta acaatgtttc ttctgataag attggtgata aaggcctttc 7600 tatgccagga gtccccaaag ctccacccat ggatctgcca gcaagtagaa 7650 aggaattaca ggcaccacgg aaacgcacag tcaaagtgac actgacacct 7700 ctaaaaatgg aaaatgagag tcaatccaaa aatgccctga aagaaagtag 7750 tcctgcttcc cctttgcaaa tagagtcaac atctcccaca gaaccaattt 7800 aaatccagga cagcctctga gatggtccag tggcccaacc aagccccaat 7850 aatacctcat gccaggattc tcaaagtaac aactatcaga atcttccagt 7900 acaggacaga aacctaatgc ttccagatgg ccccaaacct caggaggatg 7950 gctcttttaa aaggaggtat ccccgtcgca gtgcccgtgc acgttctaac 8000 atgttttttg ggcttacccc actctatgga gtaagatcct atggtgaaga 8050 ttctacagca agacattcca gctcaactgg gaagaagcga ggcaagagat 8100 cagctgaagg acaggtggat ggggccgatg acttaagcac ttcagatgaa 8150 actattacaa gacgacttat cttcactaga acagt gattt cttcaggtgg 8200 agaggaacga ctggcatccc ataatttatt tcgggaggag gaacagtgtg 8250 atcttccaaa aatctcacag ttggatggtg ttgatgatgg gacagagagt 8300 gatactagtg tcacagccac aacaaggaaa agcagccaga ttccaaaaag 8350 gaaaatggaa aaatggtaaa cagagaactt aaagattgat agacctgaag 8400 atgctgggga gaaagaacat gtcactaaga gttctgttgg ccacaaaaat 8450 gagccaaaga tggataactg ccattctgta agcagagtta aaacacaggg 8500 acaagattcc ttggaagctc agctcagctc attggagtca agccgcagag 8550 tccacacaag taccccctcc gacaaaaatt tactggacac ctataatact 8600 gagctcctga aatcagattc agacaataac aacagtgatg actgtgggaa 8650 tatcctgcct tcagacatta tggactttgt actaaagaat actccatcca 8700 tgcaggcttt gggtgagagc ccagagtcat cttcatcaga actcctgaat 8750 cttggtgaag gattgggtct tgacagtaat cgtgaaaaag acatgggtct 8800 ttttgaagta ttttctcagc agctgcctac aacagaacct gtggatagta 8850 ctctatctca gtgtctcttc gcagaggaac agtttgagtt gcctctagag 8900 ctaccatctg atctgtctgt cttgaccacc cggagtccca ctgtccccag 8950 ccagaatccc agtagactag ctgttatctc agactcaggg gagaagagag 9000 t aaccatcac agaaaaatct gtagcctcct ctgaaagtga cccagcactg 9050 ctgagcccag gagtagatcc aactcctgaa ctcctgatca ggccacatga 9100 ttttatccaa ggacacatgg atgcagacca catctctagc cctccttgtg 9150 gttcagtaga gcaaggtcat ggcaacaatc aggatttaac taggaacagt 9200 agcacccctg gccttcaggt acctgtttcc ccaactgttc ccatccagaa 9250 ccagaagtat gtgcccaatt ctactgatag tcctggcccg tctcagattt 9300 ccaatgcagc tgtccagacc actccacccc acctgaagcc agccactgag 9350 aaactcatag ttgttaacca gaacatgcag ccactttatg ttctccaaac 9400 tcttccaaat ggagtgaccc aaaaaatcca attgacctct tctgttagtt 9450 ctacacccag tgtgatggag acaaatactt cagtattggg acccatggga 9500 ggtggtctca cccttaccac aggactaaat ccaagcttgc caacttctca 9550 atctttgttc ccttctgcta gcaaaggatt gctacccatg tctcatcacc 9600 agcacttaca ttccttccct gcagctactc aaagtagttt cccaccaaac 9650 atcagcaatc ctccttcagg cctgcttatt ggggttcagc ctcctccgga 9700 tccccaactt ttggtttcag aatccagcca ctcagtacca gaggacagac 9750 cagtagccac tccatcctct ggactcaaga aaagacccat atctcgtcta ACTT 9800 agaataaaaa cagacccgaa gctccc tctagtaccc cttcaaacat 9850 tgccccttct gatgtggttt ctaatatgac attgattaac ttcacaccct 9900 cccagcttcc taatcatcca agtctgttag atttggggtc acttaatact 9950 tcatctcacc gaactgtccc aaaagatcta caacatcata aatctagcat 10000 catgtatttt gaaccggcac ccctgttacc acagagtgtg ggaggaactg 10050 ggcaggcaca ctgccacagc tcaacaataa gccaggatac tagccacctc 10100 acatcagggt ctgtgtctgg cttggcatcc agttcctctg tcttgaatgt 10150 tgtatccatg caaactacca caacccctac aagtagtgcg tcagttccag 10200 gacacgtcac cttaaccaac ccaaggttgc ttggtacccc agatattggc tcaataagca 10250 10300 atcttttaat caaagctagc cagcagagcc tggggattca ggaccagcct gtggctttac cgccaagttc aggaatgttt ccacaactgg ggacatcaca gaccccctct 10350 10400 actgctgcaa taacagcggc atctagcatc tgtgtgctcc cctccactca gactacgggc ataacagccg cttcaccttc gacgaacact tggggaagca 10450 10500 atcagcttca gcatgtgaac cagctccttg ccagcaaaac tgggattcat tcttcccagc ttctgcttca gtgatcttga gggccccagg tatccaactt 10550 10600 tacccagacg gtagacgctc ctaatagcat gggactggag cagaacaagg ctttatcctc agctg tgcaa gccagcccca 10650 gggttctcca cctctcctgg tcctctccat cttctggaca gcggtcagca 10700 agcccttcag tgccgggtcc cactaaaccc aaaccaaaaa ccaaacggtt 10750 tcagctgcct ctagacaaag ggaatggcaa gaagcacaaa gtttcccatt 10800 tgcggaccag ttcttctgaa gcacacattc cagaccaaga aacgacatcc 10850 ctgacctcag gcacagggac tccaggagca gaggctgagc agcaggatac 10900 agctagcgtg gagcagtcct cccagaagga gtgtgggcaa cctgcagggc 10950 tcttccggaa aagtcgctgt gttcaggtga cccaaaatcc agcaaatgaa 11000 cagaacctaa caagaaagtg gaagaggaaa aacagtggaa gtaatttcag 11050 ctccccactg atgctttggc ttcagcaaga acaaaagcgg aaggaaagca ttactgagaa 11100 11150 aaaacccaag aaaggacttg tttttgaaat ttccagtgat gatggctttc agatctgtgc agaaagtatt gaagatgcct ggaagtcatt gacagataaa gtccaggaag 11200 11250 ctcgatcaaa tgcccgccta aagcagctct catttgcagg tgttaacggt ttgaggatgc tggggattct ccatgatgca gttgtgttcc tcattgagca 11300 11350 gctgtctggt gccaagcact gtcgaaatta caaattccgt ttccacaagc cagaggaggc caatgaaccc cccttgaacc 11400 ctcacggctc agccagggct gaagtccacc tcaggaagtc ag catttgac 11450 atgtttaact tcctggcttc taaacatcgt cagcctcctg aatacaaccc 11500 caatgatgaa gaagaggagg aggtacagct gaagtcagct cggagggcaa 11550 ctagcatgga tctgccaatg cccatgcgct tccggcactt aaaaaagact 11600 tctaaggagg cagttggtgt ctacaggtct cccatccatg gccggggtct 11650 tttctgtaag agaaacattg atgcaggtga gatggtgatt gagtatgccg 11700 gcaacgtcat ccgctccatc cagactgaca agcgggaaaa gtattacgac 11750 ttggttgcta agcaagggca tatgttccga attgatgact cagaggtagt 11800 ggatgccacc atgcatggaa atgctgcacg cttcatcaat cactcgtgtg 11850 agcctaactg ctattctcgg gtcatcaata ttgatgggca gaagcacatt ccatgcgtaa 11900 11950 gtcatctttg ggagaggaac gatctaccga tcacttacga ctataagttc cccattgagg atgccagcaa caagctgccc tgcaactgtg gcgccaagaa atgccggaag 12000 12050 ttcctaaact aaagctgctc ttctccccca gtgttggagt gcaaggaggc ggggccatcc aaagcaacgc tgaaggcctt ttccagcagc tgggagctcc 12100 12150 cggattgcgt ggcacagctg aggggcctct agctctctta gtgatggctg tgtcctatac tcacatcaga catgtgatca 12200 tagtcccaga gacagagttg aggtctcgaa gaaaagatcc atgatcggct 12250 ttctcctggg gcccctccaa ttgtttactg ttagaaagtg ggaatggggt 12300 cttgcctgga ccctagcaga aggagcctat tatagagggt tggttatgtt 12350 gggagattgg gcctgaattt ctccacagaa ataagttgcc atcctcaggt 12400 tggccctttc ccaagcactg taagtgagtg ggtcaggcaa agccccaaat 12450 ggagggttgg ttagattcct gacagtttgc cagccaggcc ccacctacag 12500 cgtctgtcga acaaacagag gtctggtggt tttccctact atcctcccac 12550 tcgagagttc acttctggtt gggagacagg attcctagca cctccggtgt 12600 caaaaggctg tcatggggtt gtgccaatta attaccaaac attgagcctg 12650 caggctttga gtgggagtgt tgcccccagg agccttatct cagccaatta cctttcttga cagtaggagc 12700 12750 ggcttccctc tcccattccc tcttcactcc cttttcttcc tttcccctgt cttcatgcca ctgctttccc atgcttcttt cgggttgtag gggagactga 12800 12850 ctgcctgctc aaggacactc cctgctgggc ataggatgtg cctgcaaaaa gttccctgag cctgtaagca ctccaggtgg ggaagtggac aggagccatt 12900 12950 ggtcataacc agacagaatt tggaaacatt tccatggaga ttcataaagc gttttaaaga aacatatgta gcatgatttt gtaggagagg aaaaagatta 13000 13050 tttaaatagg atttaaatca tgcaacaacg agagtatcac agccaggatg acccttgggt cccattccta agacatggtt 13100 actttatttt ccccttgtta agacatagga agacttaatt tttaaacggt 13150 cagtgtccag ttgaaggcag aacactaatc agatttcaag gcccacaact 13200 tggggactag accaccttat gttgagggaa ctctgccacc tgcgtgcaac 13250 agtaaattca ccacagctaa atgacactac tgccctgatt actccttagg 13300 aacagcatca atgtggtcaa aatgtttctt ctcttccttt ccccaagaca 13350 gagtcctgaa cctgttaaat taagtcattg gattttactc tgttctgttt 13400 acagtttact atttaaggtt ttataaatgt aaatatattt tgtatatttt 13450 gcacttcata tctatgagaa gggagaagca cttatgacaa ggctattttt taaaccgcgg 13500 13550 tattatccta atttaaaaga agatcggttt ttaataattt tttattttca taggatgaag ttagagaaaa tattcagctg tacacacaaa gtctggtttt tcctgcccaa 13600 13650 cttccccctg gaaggtgtac tttttgttgt ttaatgtgta gcttgtttgt gccctgttga cataaatgtt tcctgggttt aataaatgga gctctttgac 13700 13750 cacccaactc gaaggaaggt cattgggcca ctcccctcct tcccctattg aaaggctaca aagctcctca gtaatatctt gatacaacag attctcttct 13800 13850 ttcccgcctc tctcctttcc ggcgcaactt ccagagtg gt gggagacggc aatctttaca tttccctcat ctttcttact 13900 tcagagttag caaacaacaa gttgaatggc aacttgacat ttttgcatca 13950 ccatctgcct cataggccac tctttccttt ccctctgccc accaagtcct 14000 catatctgca gagaacccat tgatcacctt gtgccctctt ttggggcagc 14050 ctgttgaaac tgaagcacag tctgaccact cacgataaag cagatttttc 14100 tctgcctctg ccacaaggtt tcagagtagt gtagtccaag tagagggtgg 14150 tctcgccgca ggcacccttt tcctatggaa agaagcccat gtctagcaaa 14200 gcaatacgac tcagcccagc actctctgcc ccaggactca tggctctgct 14250 gtgccttcca tcctgggctc ccttctctcc tgtgacctta agaactttgt ctggtggctt 14300 14350 tgctggaaca ttgtcactgt tttcactgtc atgcagggag cccagcactg tggccaggat ggcagagact tccttgtcat catggagaag tgccagcagg ggactgggaa 14400 14450 aagcactcta cccagacctc acctcccttc ctccttttgc ccatgaacaa gatgcagtgg ccctaggggt tccactagtg tctgctttcc tttattattg 14500 14550 cactgtgtga ggtttttttg taaatccttg tattcctatt ttttttaaag aaccttaagc tgcatttgtt aaaaaaaaaa 14600 actgaaatga ttaatgcact gatgggtcct gaattcacct tgagaaagac 14650 ccaaaggcca gtcagg GGGT ggggggaact gacctagtta cagctaaata 14700 ctgccctgct aggccatgct gtactgtgag ctctctacca cccctcctca 14750 accctaaacc ctgaggacag gggaggaacc cacagcttcc ttctcctgcc 14800 agctgcagat ggtttgcctt gcctttccac cccctaattg tcaaccacaa 14850 aaatgagaaa ttcctcttct agctcagcct tgagtccatt gccaaatttt 14900 cagcacacct gccagcaact tgggggaata agcgaaggtt tccctacaag 14950 agggaaagaa ggcaaaaacg gcacagctat ctccaaacac atctgagttc 15000 atttcaaaag tgaccaaggg aatctccgca gattgaggaa caaaagtgca 15050 tcattcccaa ttgtgatggg gaatccccca to 15081

<210> 12 <210> 12

<211> 9009 <211> 9009

<212> ADN <212> DNA

<213> Homo sapiens <213> Homo sapiens

<400> 12 <400> 12

ctccccctcc cgctcggcgc tgacccccca tccccacccc cgtgggaaca 50 ctccccctcc cgctcggcgc tgacccccca tccccacccc cgtgggaaca 50

ctgggagcct gcactccaca gaccctctcc ttgcctcttc cctcacctca 100 ctgggagcct gcactccaca gaccctctcc ttgcctcttc cctcacctca 100

gcctccgctc cccgccctct tcccggccca gggcgccggc ccacccttcc 150 gcctccgctc cccgccctct tcccggccca gggcgccggc ccacccttcc 150

ctccgccgcc ccccggccgc ggggaggaca tggccgcgca caggccggtg 200 ctccgccgcc ccccggccgc ggggaggaca tggccgcgca caggccggtg 200

gaatgggtcc aggccgtggt cagccgcttc gacgagcagc ttccaataaa 250 gaatgggtcc aggccgtggt cagccgcttc gacgagcagc ttccaataaa 250

aacaggacag cagaacacac ataccaaagt cagtactgag cacaacaagg 300 aacaggacag cagaacacac ataccaaagt cagtactgag cacaacaagg 300

aatgtctaat caatatttcc aaatacaagt tttctttggt tataagcggc 350 aatgtctaat caatatttcc aaatacaagt tttctttggt tataagcggc 350

ctcactacta ttttaaagaa tgttaacaat atgagaatat ttggagaagc 400 ctcactacta ttttaaagaa tgttaacaat atgagaatat ttggagaagc 400

tgctgaaaaa aatttatatc tctctcagtt gattatattg gatacactgg 450 tgctgaaaaa aatttatatc tctctcagtt gattatattg gatacactgg 450

aaaaatgtct tgctgggcaa ccaaaggaca caatgagatt agatgaaacg 500 aaaaatgtct tgctgggcaa ccaaaggaca caatgagatt agatgaaacg 500

atgctggtca aacagttgct gccagaaatc tgccattttc ttcacacctg 550 atgctggtca aacagttgct gccagaaatc tgccattttc ttcacacctg 550

tcgtgaagga aaccagcatg cagctgaact tcggaattct gcctctgggg 600 tcgtgaagga aaccagcatg cagctgaact tcggaattct gcctctgggg 600

ttttattttc tctcagctgc aacaacttca atgcagtctt tagtcgcatt 650 ttttattttc tctcagctgc aacaacttca atgcagtctt tagtcgcatt 650

tctaccaggt tacaggaatt aactgtttgt tcagaagaca atgttgatgt 700 tctaccaggt tacaggaatt aactgtttgt tcagaagaca atgttgatgt 700

tcatgatata gaattgttac agtatatcaa tgtggattgt gcaaaattaa 750 tcatgatata gaattgttac agtatatcaa tgtggattgt gcaaaattaa 750

aacgactcct gaaggaaaca gcatttaaat ttaaagccct aaagaaggtt 800 aacgactcct gaaggaaaca gcatttaaat ttaaagccct aaagaaggtt 800

gcgcagttag cagttataaa tagcctggaa aaggcatttt ggaactgggt 850 gcgcagttag cagttataaa tagcctggaa aaggcatttt ggaactgggt 850

agaaaattat ccagatgaat ttacaaaact gtaccagatc ccacagactg 900 atatggctga atgtgcagaa aagctatttg acttggtgga tggttttgct 950 gaaagcacca aacgtaaagc agcagtttgg ccactacaaa tcattctcct 1000 tatcttgtgt ccagaaataa tccaggatat atccaaagac gtggttgatg 1050 aaaacaacat gaataagaag ttatttctgg acagtctacg aaaagctctt 1100 gctggccatg gaggaagtag gcagctgaca gaaagtgctg caattgcctg 1150 tgtcaaactg tgtaaagcaa gtacttacat caattgggaa gataactctg 1200 tcattttcct acttgttcag tccatggtgg ttgatcttaa gaacctgctt 1250 tttaatccaa gtaagccatt ctcaagaggc agtcagcctg cagatgtgga 1300 tctaatgatt gactgccttg tttcttgctt tcgtataagc cctcacaaca 1350 accaacactt taagatctgc ctggctcaga attcaccttc tacatttcac 1400 tatgtgctgg taaattcact ccatcgaatc atcaccaatt ccgcattgga 1450 ttggtggcct aagattgatg ctgtgtattg tcactcggtt gaacttcgaa 1500 atatgtttgg tgaaacactt cataaagcag tgcaaggttg tggagcacac 1550 ccagcaatac gaatggcacc gagtcttaca tttaaagaaa aagtaacaag 1600 ccttaaattt aaagaaaaac ctacagacct ggagacaaga agctataagt 1650 atcttctctt gtccatggtg aaactaattc atgcagatcc aaagctcttg 1700 ctttgtaatc caagaaaaca ggggcccgaa acccaaggca gtacagcaga 1750 attaattaca gggctcgtcc aactggtccc tcagtcacac atgccagaga 1800 ttgctcagga agcaatggag gctctgctgg ttcttcatca gttagatagc 1850 attgatttgt ggaatcctga tgctcctgta gaaacatttt gggagattag 1900 ctcacaaatg cttttttaca tctgcaagaa attaactagt catcaaatgc 1950 ttagtagcac agaaattctc aagtggttgc gggaaatatt gatctgcagg 2000 aataaatttc ttcttaaaaa taagcaggca gatagaagtt cctgtcactt 2050 tctccttttt tacggggtag gatgtgatat tccttctagt ggaaatacca 2100 gtcaaatgtc catggatcat gaagaattac tacgtactcc tggagcctct 2150 ctccggaagg gaaaagggaa ctcctctatg gatagtgcag caggatgcag 2200 cggaaccccc ccgatttgcc gacaagccca gaccaaacta gaagtggccc 2250 tgtacatgtt tctgtggaac cctgacactg aagctgttct ggttgccatg 2300 tcctgtttcc gccacctctg tgaggaagca gatatccggt gtggggtgga 2350 tgaagtgtca gtgcataacc tcttgcccaa ctataacaca ttcatggagt 2400 ttgcctctgt cagcaatatg atgtcaacag gaagagcagc acttcagaaa 2450 agagtgatgg cactgctgag gcgcattgag catcccactg caggaaacac 2500 tgaggcttgg gaagatacac atgcaaaatg ggaacaagca acaaagctaa 2550 tccttaacta tccaaaagcc aaaatggaag atggccaggc tgctgaaagc 2600 cttcacaaga ccattgttaa gaggcgaatg tcccatgtga gtggaggagg 2650 atccatagat ttgtctgaca cagactccct acaggaatgg atcaacatga 2700 ctggcttcct ttgtgccctt gggggagtgt gcctccagca gagaagcaat 2750 tctggcctgg caacctatag cccacccatg ggtccagtca gtgaacgtaa 2800 gggttctatg atttcagtga tgtcttcaga gggaaacgca gatacacctg 2850 tcagcaaatt tatggatcgg ctgttgtcct taatggtgtg taaccatgag 2900 aaagtgggac ttcaaatacg gaccaatgtt aaggatctgg tgggtctaga 2950 attgagtcct gctctgtatc caatgctatt taacaaattg aagaatacca 3000 tcagcaagtt ttttgactcc caaggacagg ttttattgac tgataccaat 3050 actcaatttg tagaacaaac catagctata atgaagaact tgctagataa 3100 tcatactgaa ggcagctctg aacatctagg gcaagctagc attgaaacaa 3150 tgatgttaaa tctggtcagg tatgttcgtg tgcttgggaa tatggtccat 3200 gcaattcaaa taaaaacgaa actgtgtcaa ttagttgaag taatgatggc 3250 aaggagagat gacctctcat tttgccaaga gatgaaattt aggaataaga 3300 tggtagaata cctgacagac tgggttatgg gaacatcaaa ccaagcagca 3350 gatgatgatg taaaatgtct tacaagagat ttggaccagg caagcatgga 3400 agcagtagtt tcacttctag ctggtctccc tctgcagcct gaagaaggag 3450 atggtgtgga attgatggaa gccaaatcac agttatttct taaatacttc 3500 acattattta tgaacctttt gaatgactgc agtgaagttg aagatgaaag 3550 tgcgcaaaca ggtggcagga aacgtggcat gtctcggagg ctggcatcac 3600 tgaggcactg tacggtcctt gcaatgtcaa acttactcaa tgccaacgta 3650 gacagtggtc tcatgcactc cataggctta ggttaccaca aggatctcca 3700 gacaagagct acatttatgg aagttctgac aaaaatcctt caacaaggca 3750 cagaatttga cacacttgca gaaacagtat tggctgatcg gtttgagaga 3800 ttggtggaac tggtcacaat gatgggtgat caaggagaac tccctatagc 3850 gatggctctg gccaatgtgg ttccttgttc tcagtgggat gaactagctc 3900 gagttctggt tactctgttt gattctcggc atttactcta ccaactgctc 3950 tggaacatgt tttctaaaga agtagaattg gcagactcca tgcagactct 4000 cttccgaggc aacagcttgg ccagtaaaat aatgacattc tgtttcaagg 4050 tatatggtgc tacctatcta caaaaactcc tggatccttt attacgaatt 4100 gtgatcacat cctctgattg gcaacatgtt agctttgaag tggatcctac 4150 caggttagaa ccatcagaga gccttgagga aaaccagcgg aacctccttc 4200 agatgactga aaagttcttc catgccatca tcagttcctc ctcagaattc 4250 ccccctcaac ttcgaagtgt gtgccactgt ttataccagg caacttgcca 4300 ctccctactg aataaagcta cagtaaaaga aaaaaaggaa aacaaaaaat 4350 cagtggttag ccagcgtttc cctcagaaca gcatcggtgc agtaggaagt 4400 gccatgttcc tcagatttat caatcctgcc attgtctcac cgtatgaagc 4450 agggatttta gataaaaagc caccacctag aatcgaaagg ggcttgaagt 4500 taatgtcaaa gatacttcag agtattgcca atcatgttct cttcacaaaa 4550 gaagaacata tgcggccttt caatgatttt gtgaaaagca actttgatgc 4600 agcacgcagg tttttccttg atatagcatc tgattgtcct acaagtgatg 4650 cagtaaatca tagtctttcc ttcataagtg acggcaatgt gcttgcttta 4700 catcgtctac tctggaacaa tcaggagaaa attgggcagt atctttccag 4750 caacagggat cataaagctg ttggaagacg accttttgat aagatggcaa 4800 cacttcttgc atacctgggt cctccagagc acaaacctgt ggcagataca 4850 cactggtcca gccttaacct taccagttca aagtttgagg aatttatgac 4900 taggcatcag gtacatgaaa aagaagaatt caaggctttg aaaacgttaa 4950 gtattttcta ccaagctggg acttccaaag ctgggaatcc tattttttat 5000 tatgttgcac ggaggttcaa aactggtcaa atcaatggtg atttgctgat 5050 ataccatgtc ttactgactt taaagccata ttatgcaaag ccatatgaaa 5100 ttgtagtgga ccttacccat accgggccta gcaatcgctt taaaacagac 5150 tttctctcta agtggtttgt tgtttttcct ggctttgctt acgacaacgt 5200 ctccgcagtc tatatctata actgtaactc ctgggtcagg gagtacacca 5250 agtatcatga gcggctgctg actggcctca aaggtagcaa aaggcttgtt 5300 ttcatagact gtcctgggaa actggctgag cacatagagc atgaacaaca 5350 gaaactacct gctgccacct tggctttaga agaggacctg aaggtattcc 5400 acaatgctct caagctagct cacaaagaca ccaaagtttc tattaaagtt 5450 ggttctactg ctgtccaagt aacttcagca gagcgaacaa aagtcctagg 5500 gcaatcagtc tttctaaatg acatttatta tgcttcggaa attgaagaaa 5550 tctgcctagt agatgagaac cagttcacct taaccattgc aaaccagggc 5600 acgccgctca ccttcatgca ccaggagtgt gaagccattg tccagtctat 5650 cattcatatc cggacccgct gggaactgtc acagcccgac tctatccccc 5700 aacacaccaa gattcggcca aaagatgtcc ctgggacact gctcaatatc 5750 gcattactta atttaggcag ttctgacccg agtttacggt cagctgccta 5800 taatcttctg tgtgccttaa cttgtacctt taatttaaaa atcgagggcc 5850 agttactaga gacatcaggt ttatgtatcc ctgccaacaa caccctcttt 5900 attgtctcta ttagtaagac actggcagcc aatgagccac acctcacgtt 5950 agaatttttg gaagagtgta tttctggatt tagcaaatct agtattgaat 6000 tgaaacacct ttgtttggaa tacatgactc catggctgtc aaatctagtt 6050 cgtttttgca agcataatga tgatgccaaa cgacaaagag ttactgctat 6100 tcttgacaag ctgataacaa tgaccatcaa tgaaaaacag atgtacccat 6150 ctattcaagc aaaaatatgg ggaagccttg ggcagattac agatctgctt 6200 gatgttgtac tagacagttt catcaaaacc agtgcaacag gtggcttggg 6250 atcaataaaa gctgaggtga tggcagatac tgctgtagct ttggcttctg 6300 gaaatgtgaa attggtttca agcaaggtta ttggaaggat gtgcaaaata 6350 attgacaaga catgcttatc tccaactcct actttagaac aacatcttat 6400 gtgggatgat attgctattt tagcacgcta catgctgatg ctgtccttca 6450 acaattccct tgatgtggca gctcatcttc cctacctctt ccacgttgtt 6500 actttcttag tagccacagg tccgctctcc cttagagctt ccacacatgg 6550 actggtcatt aatatcattc actctctgtg tacttgttca cagcttcatt 6600 ttagtgaaga gaccaagcaa gttttgagac tcagtctgac agagttctca 6650 ttacccaaat tttacttgct gtttggcatt agcaaagtca agtcagctgc 6700 tgtcattgcc ttccgttcca gttaccggga caggtcattc tctcctggct 6750 cctatgagag agagactttt gctttgacat ccttggaaac agtcacagaa 6800 gctttgttgg agatcatgga ggcatgcatg agagatattc caacgtgcaa 6850 gtggctggac cagtggacag aactagctca aagatttgca ttccaatata 6900 atccatccct gcaaccaaga gctcttgttg tctttgggtg tattagcaaa 6950 cgagtgtctc atgggcagat aaagcagata atccgtattc ttagcaaggc 7000 acttgagagt tgcttaaaag gacctgacac ttacaacagt caagttctga 7050 tagaagctac agtaatagca ctaaccaaat tacagccact tcttaataag 7100 gactcgcctc tgcacaaagc cctcttttgg gtagctgtgg ctgtgctgca 7150 gcttgatgag gtcaacttgt attcagcagg taccgcactt cttgaacaaa 7200 acctgcatac tttagatagt ctccgtatat tcaatgacaa gagtccagag 7250 gaagtattta tggcaatccg gaatcctctg gagtggcact gcaagcaaat 7300 ggatcatttt gttggactca atttcaactc taactttaac tttgcattgg 7350 ttggacacct tttaaaaggg tacaggcatc cttcacctgc tattgttgca 7400 agaacagtca gaattttaca tacactacta actctggtta acaaacacag 7450 aaattgtgac aaatttgaag tgaatacaca gagcgtggcc tacttagcag 7500 ctttacttac agtgtctgaa gaagttcgaa gtcgctgcag cctaaaacat 7550 agaaagtcac ttcttcttac tgatatttca atggaaaatg ttcctatgga 7600 tacatatccc attcatcatg gtgacccttc ctataggaca ctaaaggaga 7650 ctcagccatg gtcctctccc aaaggttctg aaggatacct tgcagccacc 7700 tatccaactg tcggccagac cagtccccga gccaggaaat ccatgagcct 7750 ggacatgggg caaccttctc aggccaacac taagaagttg cttggaacaa 7800 ggaaaagttt tgatcacttg atatcagaca caaaggctcc taaaaggcaa 7850 gaaatggaat cagggatcac aacacccccc aaaatgagga gagtagcaga 7900 aactgattat gaaatggaaa ctcagaggat ttcctcatca caacagcacc 7950 cacatttacg taaagtttca gtgtctgaat caaatgttct cttggatgaa 8000 gaagtactta ctgatccgaa gatccaggcg ctgcttctta ctgttctagc 8050 tacactggta aaatatacca cagatgagtt tgatcaacga attctttatg 8100 aatacttagc agaggccagt gttgtgtttc ccaaagtctt tcctgttgtg 8150 cataatttgt tggactctaa gatcaacacc ctgttatcat tgtgccaaga 8200 tccaaatttg ttaaatccaa tccatggaat tgtgcagagt gtggtgtacc 8250 atgaagaatc cccaccacaa taccaaacat cttacctgca aagttttggt 8300 tttaatggct tgtggcggtt tgcaggaccg ttttcaaagc aaacacaaat 8350 tccagactat gctgagctta ttgttaagtt tcttgatgcc ttgattgaca 8400 cgtacctgcc tggaattgat gaagaaacca gtgaagaatc cctcctgact 8450 cccacatctc cttaccctcc tgcactgcag agccagctta gtatcactgc 8500 caaccttaac ctttctaatt ccatgacctc acttgcaact tcccagcatt 8550 ccccaggaat cgacaaggag aacgttgaac tctcccctac cactggccac 8600 tgtaacagtg gacgaactcg ccacggatcc gcaagccaag tgcagaagca 8650 aagaagcgct ggcagtttca aacgtaatag cattaagaag atcgtgtgaa 8700 gcttgcttgc tttctttttt aaaatcaact taacatgggc tcttcactag 8750 tgaccccttc cctgtccttg ccctttcccc ccatgttgta atgctgcact 8800 tcctgtttta taatgaaccc atccggtttg ccatgttgcc agatgatcaa 8850 ctcttcgaag ccttgcctaa atttaatgct gccttttctt taactttttt 8900 tcttctactt ttggcgtgta tctggtatat gtaagtgttc agaacaactg 8950 caaagaaagt gggaggtcag gaaactttta actgagaaat ctcaattgta 9000 agagaggat 9009 agaaaattat ccagatgaat ttacaaaact gtaccagatc ccacagactg 900 atgtgcagaa atatggctga aagctatttg acttggtgga tggttttgct 950 gaaagcacca aacgtaaagc agcagtttgg ccactacaaa tcattctcct 1000 tatcttgtgt ccagaaataa tccaggatat atccaaagac gtggttgatg 1050 aaaacaacat gaataagaag ttatttctgg acagtctacg aaaagctctt 1100 gctggccatg gaggaagtag gcagctgaca gaaagtgctg caattgcctg 1150 tgtcaaactg tgtaaagcaa gtacttacat caattgggaa gataactctg 1200 tcattttcct acttgttcag tccatggtgg ttgatcttaa gaacctgctt 1250 tttaatccaa gtaagccatt ctcaagaggc agtcagcctg cagatgtgga 1300 tctaatgatt gactgccttg tttcttgctt tcgtataagc cctcacaaca 1350 accaacactt taagatctgc ctggctcaga attcaccttc tacatttcac 1400 tatgtgctgg taaattcact ccatcgaatc atcaccaatt ccgcattgga 1450 ttggtggcct aagattgatg ctgtgtattg tcactcggtt gaacttcgaa 1500 atatgtttgg tgaaacactt cataaagcag tgcaaggttg tggagcacac 1550 ccagcaatac gaatggcacc gagtcttaca tttaaagaaa aagtaacaag 1600 ccttaaattt aaagaaaaac ctacagacct ggagacaaga agctataagt 1650 atcttctctt gtccatggtg aaact AATTC atgcagatcc aaagctcttg 1700 caagaaaaca ctttgtaatc acccaaggca ggggcccgaa gtacagcaga 1750 attaattaca gggctcgtcc aactggtccc tcagtcacac atgccagaga 1800 ttgctcagga agcaatggag gctctgctgg ttcttcatca gttagatagc 1850 ggaatcctga attgatttgt tgctcctgta gaaacatttt gggagattag 1900 cttttttaca ctcacaaatg tctgcaagaa attaactagt catcaaatgc 1950 ttagtagcac agaaattctc aagtggttgc gggaaatatt gatctgcagg 2000 aataaatttc ttcttaaaaa taagcaggca gatagaagtt cctgtcactt 2050 tctccttttt tacggggtag gatgtgatat tccttctagt ggaaatacca 2100 gtcaaatgtc catggatcat gaagaattac tacgtactcc tggagcctct 2150 ctccggaagg gaaaagggaa ctcctctatg gatagtgcag caggatgcag 2200 cggaaccccc ccgatttgcc gaccaaacta gacaagccca gaagtggccc 2250 tgtacatgtt tctgtggaac cctgacactg aagctgttct ggttgccatg 2300 tcctgtttcc gccacctctg tgaggaagca gatatccggt gtggggtgga 2350 tgaagtgtca gtgcataacc tcttgcccaa ctataacaca ttcatggagt 2400 ttgcctctgt cagcaatatg atgtcaacag gaagagcagc acttcagaaa 2450 agagtgatgg cactgctgag gcgcattgag catcccactg caggaaa cac 2500 tgaggcttgg gaagatacac atgcaaaatg ggaacaagca acaaagctaa 2550 tccttaacta tccaaaagcc aaaatggaag atggccaggc tgctgaaagc 2600 ccattgttaa cttcacaaga gaggcgaatg tcccatgtga gtggaggagg 2650 atccatagat ttgtctgaca cagactccct acaggaatgg atcaacatga 2700 ctggcttcct ttgtgccctt gggggagtgt gcctccagca gagaagcaat 2750 tctggcctgg caacctatag cccacccatg ggtccagtca gtgaacgtaa 2800 atttcagtga gggttctatg tgtcttcaga gggaaacgca gatacacctg 2850 tcagcaaatt tatggatcgg ctgttgtcct taatggtgtg taaccatgag 2900 aaagtgggac ttcaaatacg gaccaatgtt aaggatctgg tgggtctaga 2950 attgagtcct gctctgtatc caatgctatt taacaaattg aagaatacca 3000 tcagcaagtt ttttgactcc caaggacagg ttttattgac tgataccaat 3050 actcaatttg tagaacaaac catagctata atgaagaact tgctagataa 3100 tcatactgaa ggcagctctg aacatctagg gcaagctagc attgaaacaa 3150 tgatgttaaa tctggtcagg tatgttcgtg tgcttgggaa tatggtccat 3200 taaaaacgaa gcaattcaaa actgtgtcaa ttagttgaag taatgatggc 3250 aaggagagat gacctctcat tttgccaaga gatgaaattt aggaataaga 3300 tggtagaata cct gacagac tgggttatgg gaacatcaaa ccaagcagca 3350 gatgatgatg taaaatgtct tacaagagat ttggaccagg caagcatgga 3400 agcagtagtt tcacttctag ctggtctccc tctgcagcct gaagaaggag 3450 attgatggaa atggtgtgga gccaaatcac agttatttct taaatacttc 3500 acattattta tgaacctttt gaatgactgc agtgaagttg aagatgaaag 3550 ggtggcagga tgcgcaaaca aacgtggcat gtctcggagg ctggcatcac 3600 tgaggcactg tacggtcctt gcaatgtcaa acttactcaa tgccaacgta 3650 tcatgcactc gacagtggtc cataggctta ggttaccaca aggatctcca 3700 gacaagagct acatttatgg aagttctgac aaaaatcctt caacaaggca 3750 cacacttgca cagaatttga gaaacagtat tggctgatcg gtttgagaga 3800 ttggtggaac tggtcacaat gatgggtgat caaggagaac tccctatagc 3850 gatggctctg gccaatgtgg ttccttgttc tcagtgggat gaactagctc 3900 gagttctggt tactctgttt gattctcggc atttactcta ccaactgctc 3950 tggaacatgt tttctaaaga agtagaattg gcagactcca tgcagactct 4000 cttccgaggc aacagcttgg ccagtaaaat aatgacattc tgtttcaagg 4050 tatatggtgc tacctatcta caaaaactcc tggatccttt attacgaatt 4100 gtgatcacat cctctgattg gcaacatgtt agctt tgaag tggatcctac 4150 ccatcagaga caggttagaa gccttgagga aaaccagcgg aacctccttc 4200 agatgactga aaagttcttc catgccatca tcagttcctc ctcagaattc 4250 ccccctcaac ttcgaagtgt gtgccactgt ttataccagg caacttgcca 4300 aataaagcta ctccctactg cagtaaaaga aaaaaaggaa aacaaaaaat 4350 cagtggttag ccagcgtttc cctcagaaca gcatcggtgc agtaggaagt 4400 gccatgttcc tcagatttat caatcctgcc attgtctcac cgtatgaagc 4450 agggatttta gataaaaagc caccacctag aatcgaaagg ggcttgaagt 4500 taatgtcaaa gatacttcag atcatgttct agtattgcca cttcacaaaa 4550 tgcggccttt gaagaacata gtgaaaagca caatgatttt actttgatgc 4600 agcacgcagg tttttccttg atatagcatc tgattgtcct acaagtgatg 4650 cagtaaatca tagtctttcc ttcataagtg acggcaatgt gcttgcttta 4700 catcgtctac tctggaacaa tcaggagaaa attgggcagt atctttccag 4750 caacagggat cataaagctg ttggaagacg accttttgat aagatggcaa 4800 cacttcttgc atacctgggt cctccagagc acaaacctgt ggcagataca 4850 cactggtcca gccttaacct taccagttca aagtttgagg aatttatgac 4900 taggcatcag gtacatgaaa aagaagaatt caaggctttg aaaacgttaa 4950 g tattttcta ccaagctggg acttccaaag ctgggaatcc tattttttat 5000 tatgttgcac ggaggttcaa aactggtcaa atcaatggtg atttgctgat 5050 ataccatgtc ttactgactt taaagccata ttatgcaaag ccatatgaaa 5100 ttgtagtgga ccttacccat accgggccta gcaatcgctt taaaacagac 5150 tttctctcta agtggtttgt tgtttttcct ggctttgctt acgacaacgt 5200 ctccgcagtc tatatctata actgtaactc ctgggtcagg gagtacacca 5250 gcggctgctg agtatcatga aaggtagcaa actggcctca aaggcttgtt 5300 ttcatagact gtcctgggaa actggctgag atgaacaaca cacatagagc 5350 gaaactacct gctgccacct tggctttaga agaggacctg aaggtattcc 5400 caagctagct acaatgctct cacaaagaca ccaaagtttc tattaaagtt 5450 ggttctactg ctgtccaagt aacttcagca gagcgaacaa aagtcctagg 5500 gcaatcagtc tttctaaatg tgcttcggaa acatttatta attgaagaaa 5550 tctgcctagt agatgagaac cagttcacct taaccattgc aaaccagggc 5600 ccttcatgca acgccgctca ccaggagtgt gaagccattg tccagtctat 5650 cattcatatc cggacccgct gggaactgtc acagcccgac tctatccccc 5700 gattcggcca aacacaccaa aaagatgtcc ctgggacact gctcaatatc 5750 gcattactta atttaggcag TTCT gacccg agtttacggt cagctgccta 5800 taatcttctg tgtgccttaa cttgtacctt taatttaaaa atcgagggcc 5850 agttactaga gacatcaggt ttatgtatcc ctgccaacaa caccctcttt 5900 attgtctcta ttagtaagac actggcagcc aatgagccac acctcacgtt 5950 agaatttttg gaagagtgta tttctggatt tagcaaatct agtattgaat 6000 tgaaacacct ttgtttggaa tacatgactc catggctgtc aaatctagtt 6050 agcataatga cgtttttgca tgatgccaaa cgacaaagag ttactgctat 6100 tcttgacaag ctgataacaa tgaccatcaa tgaaaaacag atgtacccat 6150 ctattcaagc aaaaatatgg ggaagccttg ggcagattac agatctgctt 6200 gatgttgtac tagacagttt catcaaaacc agtgcaacag gtggcttggg 6250 gctgaggtga atcaataaaa tggcagatac tgctgtagct ttggcttctg 6300 attggtttca gaaatgtgaa agcaaggtta ttggaaggat gtgcaaaata 6350 attgacaaga catgcttatc tccaactcct actttagaac aacatcttat 6400 gtgggatgat attgctattt tagcacgcta catgctgatg ctgtccttca 6450 tgatgtggca acaattccct gctcatcttc cctacctctt ccacgttgtt 6500 actttcttag tagccacagg tccgctctcc cttagagctt ccacacatgg 6550 actggtcatt aatatcattc actctctgtg tacttgttca cagctt catt 6600 gaccaagcaa ttagtgaaga gttttgagac tcagtctgac agagttctca 6650 ttacccaaat tttacttgct gtttggcatt agcaaagtca agtcagctgc 6700 ttccgttcca tgtcattgcc gttaccggga caggtcattc tctcctggct 6750 cctatgagag agagactttt gctttgacat ccttggaaac agtcacagaa 6800 gctttgttgg agatcatgga ggcatgcatg agagatattc caacgtgcaa 6850 gtggctggac cagtggacag aactagctca aagatttgca ttccaatata 6900 atccatccct gcaaccaaga gctcttgttg tctttgggtg tattagcaaa 6950 cgagtgtctc atgggcagat aaagcagata atccgtattc ttagcaaggc 7000 acttgagagt tgcttaaaag gacctgacac ttacaacagt caagttctga 7050 tagaagctac agtaatagca ctaaccaaat tacagccact tcttaataag 7100 gactcgcctc tgcacaaagc cctcttttgg gtagctgtgg ctgtgctgca 7150 gcttgatgag gtcaacttgt attcagcagg taccgcactt cttgaacaaa 7200 acctgcatac tttagatagt ctccgtatat tcaatgacaa gagtccagag 7250 gaagtattta tggcaatccg gaatcctctg gagtggcact gcaagcaaat 7300 ggatcatttt gttggactca atttcaactc taactttaac tttgcattgg 7350 ttggacacct tttaaaaggg tacaggcatc cttcacctgc tattgttgca 7400 gaa agaacagtca ttttaca actctggtta tacactacta acaaacacag 7450 aaattgtgac aaatttgaag tgaatacaca gagcgtggcc tacttagcag 7500 agtgtctgaa ctttacttac gaagttcgaa gtcgctgcag cctaaaacat 7550 agaaagtcac ttcttcttac tgatatttca atggaaaatg ttcctatgga 7600 tacatatccc attcatcatg gtgacccttc ctataggaca ctaaaggaga 7650 ctcagccatg gtcctctccc aaaggttctg aaggatacct tgcagccacc 7700 tatccaactg tcggccagac cagtccccga gccaggaaat ccatgagcct 7750 ggacatgggg caaccttctc aggccaacac taagaagttg cttggaacaa 7800 ggaaaagttt tgatcacttg atatcagaca caaaggctcc taaaaggcaa 7850 gaaatggaat cagggatcac aacacccccc aaaatgagga gagtagcaga 7900 gaaatggaaa aactgattat ttcctcatca ctcagaggat caacagcacc 7950 taaagtttca cacatttacg gtgtctgaat caaatgttct cttggatgaa 8000 ctgatccgaa gaagtactta gatccaggcg ctgcttctta ctgttctagc 8050 aaatatacca tacactggta cagatgagtt tgatcaacga attctttatg 8100 aatacttagc agaggccagt gttgtgtttc ccaaagtctt tcctgttgtg 8150 cataatttgt tggactctaa gatcaacacc ctgttatcat tgtgccaaga 8200 tccaaatttg ttaaatccaa tccatggaat tgtgca gagt gtggtgtacc 8250 atgaagaatc cccaccacaa taccaaacat cttacctgca aagttttggt 8300 tttaatggct tgtggcggtt tgcaggaccg ttttcaaagc aaacacaaat 8350 tccagactat gctgagctta ttgttaagtt tcttgatgcc ttgattgaca 8400 cgtacctgcc tggaattgat gaagaaacca gtgaagaatc cctcctgact 8450 cccacatctc cttaccctcc tgcactgcag agccagctta gtatcactgc 8500 caaccttaac ctttctaatt ccatgacctc acttgcaact tcccagcatt 8550 ccccaggaat cgacaaggag aacgttgaac tctcccctac cactggccac 8600 tgtaacagtg gacgaactcg ccacggatcc gcaagccaag tgcagaagca 8650 aagaagcgct ggcagtttca aacgtaatag cattaagaag atcgtgtgaa 8700 gcttgcttgc tttctttttt aaaatcaact taacatgggc tcttcactag 8750 tgaccccttc cctgtccttg ccctttcccc ccatgttgta atgctgcact 8800 tcctgtttta taatgaaccc atccggtttg ccatgttgcc agatgatcaa 8850 ctcttcgaag ccttgcctaa atttaatgct gccttttctt taactttttt 8900 tcttctactt ttggcgtgta tctggtatat gtaagtgttc agaacaactg 8950 caaagaaagt gggaggtcag gaaactttta actgagaaat ctcaattgta agagaggat 9000 9009

<210> 13 <210> 13

<211> 6390 <211> 6390

<212> ADN <212> DNA

<213> Homo sapiens <213> Homo sapiens

<400> 13 <400> 13

ggtttttgag cccattactg ttggagctac agggagagaa acagaggagg 50 ggtttttgag cccattactg ttggagctac agggagagaa acagaggagg 50

agactgcaag agatcattgg aggccgtggg cacgctcttt actccatgtg 100 agactgcaag agatcattgg aggccgtggg cacgctcttt actccatgtg 100

tgggacattc attgcggaat aacatcggag gagaagtttc ccagagctat 150 tgggacattc attgcggaat aacatcggag gagaagtttc ccagagctat 150

ggggacttcc catccggcgt tcctggtctt aggctgtctt ctcacagggc 200 tgagcctaat cctctgccag ctttcattac cctctatcct tccaaatgaa 250 aatgaaaagg ttgtgcagct gaattcatcc ttttctctga gatgctttgg 300 ggagagtgaa gtgagctggc agtaccccat gtctgaagaa gagagctccg 350 atgtggaaat cagaaatgaa gaaaacaaca gcggcctttt tgtgacggtc 400 ttggaagtga gcagtgcctc ggcggcccac acagggttgt acacttgcta 450 ttacaaccac actcagacag aagagaatga gcttgaaggc aggcacattt 500 acatctatgt gccagaccca gatgtagcct ttgtacctct aggaatgacg 550 gattatttag tcatcgtgga ggatgatgat tctgccatta taccttgtcg 600 cacaactgat cccgagactc ctgtaacctt acacaacagt gagggggtgg 650 tacctgcctc ctacgacagc agacagggct ttaatgggac cttcactgta 700 gggccctata tctgtgaggc caccgtcaaa ggaaagaagt tccagaccat 750 cccatttaat gtttatgctt taaaagcaac atcagagctg gatctagaaa 800 tggaagctct taaaaccgtg tataagtcag gggaaacgat tgtggtcacc 850 tgtgctgttt ttaacaatga ggtggttgac cttcaatgga cttaccctgg 900 agaagtgaaa ggcaaaggca tcacaatgct ggaagaaatc aaagtcccat 950 ccatcaaatt ggtgtacact ttgacggtcc ccgaggccac ggtgaaagac 1000 agtggagatt acgaatgtgc tgcccgccag gctaccaggg aggtcaaaga 1050 aatgaagaaa gtcactattt ctgtccatga gaaaggtttc attgaaatca 1100 aacccacctt cagccagttg gaagctgtca acctgcatga agtcaaacat 1150 tttgttgtag aggtgcgggc ctacccacct cccaggatat cctggctgaa 1200 aaacaatctg actctgattg aaaatctcac tgagatcacc actgatgtgg 1250 aaaagattca ggaaataagg tatcgaagca aattaaagct gatccgtgct 1300 aaggaagaag acagtggcca ttatactatt gtagctcaaa atgaagatgc 1350 tgtgaagagc tatacttttg aactgttaac tcaagttcct tcatccattc 1400 tggacttggt cgatgatcac catggctcaa ctgggggaca gacggtgagg 1450 tgcacagctg aaggcacgcc gcttcctgat attgagtgga tgatatgcaa 1500 agatattaag aaatgtaata atgaaacttc ctggactatt ttggccaaca 1550 atgtctcaaa catcatcacg gagatccact cccgagacag gagtaccgtg 1600 gagggccgtg tgactttcgc caaagtggag gagaccatcg ccgtgcgatg 1650 cctggctaag aatctccttg gagctgagaa ccgagagctg aagctggtgg 1700 ctcccaccct gcgttctgaa ctcacggtgg ctgctgcagt cctggtgctg 1750 ttggtgattg tgatcatctc acttattgtc ctggttgtca tttggaaaca 1800 gaaaccgagg tatgaaattc gctggagggt cattgaatca atcagcccag 1850 atggacatga atatatttat gtggacccga tgcagctgcc ttatgactca 1900 agatgggagt ttccaagaga tggactagtg cttggtcggg tcttggggtc 1950 tggagcgttt gggaaggtgg ttgaaggaac agcctatgga ttaagccggt 2000 cccaacctgt catgaaagtt gcagtgaaga tgctaaaacc cacggccaga 2050 tccagtgaaa aacaagctct catgtctgaa ctgaagataa tgactcacct 2100 ggggccacat ttgaacattg taaacttgct gggagcctgc accaagtcag 2150 gccccattta catcatcaca gagtattgct tctatggaga tttggtcaac 2200 tatttgcata agaataggga tagcttcctg agccaccacc cagagaagcc 2250 aaagaaagag ctggatatct ttggattgaa ccctgctgat gaaagcacac 2300 ggagctatgt tattttatct tttgaaaaca atggtgacta catggacatg 2350 aagcaggctg atactacaca gtatgtcccc atgctagaaa ggaaagaggt 2400 ttctaaatat tccgacatcc agagatcact ctatgatcgt ccagcctcat 2450 ataagaagaa atctatgtta gactcagaag tcaaaaacct cctttcagat 2500 gataactcag aaggccttac tttattggat ttgttgagct tcacctatca 2550 agttgcccga ggaatggagt ttttggcttc aaaaaattgt gtccaccgtg 2600 atctggctgc tcgcaacgtc ctcctggcac aaggaaaaat tgtgaagatc 2650 tgtgactttg gcctggccag agacatcatg catgattcga actatgtgtc 2700 gaaaggcagt acctttctgc ccgtgaagtg gatggctcct gagagcatct 2750 ttgacaacct ctacaccaca ctgagtgatg tctggtctta tggcattctg 2800 ctctgggaga tcttttccct tggtggcacc ccttaccccg gcatgatggt 2850 ggattctact ttctacaata agatcaagag tgggtaccgg atggccaagc 2900 ctgaccacgc taccagtgaa gtctacgaga tcatggtgaa atgctggaac 2950 agtgagccgg agaagagacc ctccttttac cacctgagtg agattgtgga 3000 gaatctgctg cctggacaat ataaaaagag ttatgaaaaa attcacctgg 3050 acttcctgaa gagtgaccat cctgctgtgg cacgcatgcg tgtggactca 3100 gacaatgcat acattggtgt cacctacaaa aacgaggaag acaagctgaa 3150 ggactgggag ggtggtctgg atgagcagag actgagcgct gacagtggct 3200 acatcattcc tctgcctgac attgaccctg tccctgagga ggaggacctg 3250 ggcaagagga acagacacag ctcgcagacc tctgaagaga gtgccattga 3300 gacgggttcc agcagttcca ccttcatcaa gagagaggac gagaccattg 3350 aagacatcga catgatggat gacatcggca tagactcttc agacctggtg 3400 gaagacagct tcctgtaact ggcggattcg aggggttcct tccacttctg 3450 gggccacctc tggatcccgt tcagaaaacc actttattgc aatgcagagg 3500 ttgagaggag gacttggttg atgtttaaag agaagttccc agccaagggc 3550 ctcggggagc gttctaaata tgaatgaatg ggatattttg aaatgaactt 3600 tgtcagtgtt gcctcttgca atgcctcagt agcatctcag tggtgtgtga 3650 agtttggaga tagatggata agggaataat aggccacaga aggtgaactt 3700 tgtgcttcaa ggacattggt gagagtccaa cagacacaat ttatactgcg 3750 acagaacttc agcattgtaa ttatgtaaat aactctaacc aaggctgtgt 3800 ttagattgta ttaactatct tctttggact tctgaagaga ccactcaatc 3850 catccatgta cttccctctt gaaacctgat gtcagctgct gttgaacttt 3900 ttaaagaagt gcatgaaaaa ccatttttga accttaaaag gtactggtac 3950 tatagcattt tgctatcttt tttagtgtta aagagataaa gaataataat 4000 taaccaacct tgtttaatag atttgggtca tttagaagcc tgacaactca 4050 ttttcatatt gtaatctatg tttataatac tactactgtt atcagtaatg 4100 ctaaatgtgt aataatgtaa catgatttcc ctccagagaa agcacaattt 4150 aaaacaatcc ttactaagta ggtgatgagt ttgacagttt ttgacattta 4200 tattaaataa catgtttctc tataaagtat ggtaatagct ttagtgaatt 4250 aaatttagtt gagcatagag aacaaagtaa aagtagtgtt gtccaggaag 4300 tcagaatttt taactgtact gaataggttc cccaatccat cgtattaaaa 4350 aacaattaac tgccctctga aataatggga ttagaaacaa acaaaactct 4400 taagtcctaa aagttctcaa tgtagaggca taaacctgtg ctgaacataa 4450 cttctcatgt atattaccca atggaaaata taatgatcag caaaaagact 4500 ggatttgcag aagttttttt tttttttttc ttcatgcctg atgaaagctt 4550 tggcgacccc aatatatgta ttttttgaat ctatgaacct gaaaagggtc 4600 agaaggatgc ccagacatca gcctccttct ttcacccctt accccaaaga 4650 gaaagagttt gaaactcgag accataaaga tattctttag tggaggctgg 4700 atgtgcatta gcctggatcc tcagttctca aatgtgtgtg gcagccagga 4750 tgactagatc ctgggtttcc atccttgaga ttctgaagta tgaagtctga 4800 gggaaaccag agtctgtatt tttctaaact ccctggctgt tctgatcggc 4850 cagttttcgg aaacactgac ttaggtttca ggaagttgcc atgggaaaca 4900 aataatttga actttggaac agggttggca ttcaaccacg caggaagcct 4950 actatttaaa tccttggctt caggttagtg acatttaatg ccatctagct 5000 agcaattgcg accttaattt aactttccag tcttagctga ggctgagaaa 5050 gctaaagttt ggttttgaca ggttttccaa aagtaaagat gctacttccc 5100 actgtatggg ggagattgaa ctttccccgt ctcccgtctt ctgcctccca 5150 ctccataccc cgccaaggaa aggcatgtac aaaaattatg caattcagtg 5200 ttccaagtct ctgtgtaacc agctcagtgt tttggtggaa aaaacatttt 5250 aagttttact gataatttga ggttagatgg gaggatgaat tgtcacatct 5300 atccacactg tcaaacaggt tggtgtgggt tcattggcat tctttgcaat 5350 actgcttaat tgctgatacc atatgaatga aacatgggct gtgattactg 5400 caatcactgt gctatcggca gatgatgctt tggaagatgc agaagcaata 5450 ataaagtact tgactaccta ctggtgtaat ctcaatgcaa gccccaactt 5500 tcttatccaa ctttttcata gtaagtgcga agactgagcc agattggcca 5550 attaaaaacg aaaacctgac taggttctgt agagccaatt agacttgaaa 5600 tacgtttgtg tttctagaat cacagctcaa gcattctgtt tatcgctcac 5650 tctcccttgt acagccttat tttgttggtg ctttgcattt tgatattgct 5700 gtgagccttg catgacatca tgaggccgga tgaaacttct cagtccagca 5750 gtttccagtc ctaacaaatg ctcccacctg aatttgtata tgactgcatt 5800 tgtgtgtgtg tgtgtgtttt cagcaaattc cagatttgtt tccttttggc 5850 ctcctgcaaa gtctccagaa gaaaatttgc caatctttcc tactttctat 5900 ttttatgatg acaatcaaag ccggcctgag aaacactatt tgtgactttt 5950 taaacgatta gtgatgtcct taaaatgtgg tctgccaatc tgtacaaaat 6000 ggtcctattt ttgtgaagag ggacataaga taaaatgatg ttatacatca 6050 atatgtatat atgtatttct atatagactt ggagaatact gccaaaacat 6100 ttatgacaag ctgtatcact gccttcgttt atattttttt aactgtgata 6150 atccccacag gcacattaac tgttgcactt ttgaatgtcc aaaatttata 6200 ttttagaaat aataaaaaga aagatactta catgttccca aaacaatggt 6250 gtggtgaatg tgtgagaaaa actaacttga tagggtctac caatacaaaa 6300 tgtattacga atgcccctgt tcatgttttt gttttaaaac gtgtaaatga 6350 agatctttat atttcaataa atgatatata atttaaagtt 6390 ggggacttcc catccggcgt tcctggtctt aggctgtctt ctcacagggc 200 tgagcctaat cctctgccag ctttcattac cctctatcct tccaaatgaa 250 aatgaaaagg ttgtgcagct gaattcatcc ttttctctga gatgctttgg 300 ggagagtgaa gtgagctggc agtaccccat gtctgaagaa gagagctccg 350 cagaaatgaa atgtggaaat gaaaacaaca gcggcctttt tgtgacggtc 400 ttggaagtga gcagtgcctc ggcggcccac acagggttgt acacttgcta 450 ttacaaccac actcagacag aagagaatga gcttgaaggc aggcacattt 500 gccagaccca acatctatgt gatgtagcct ttgtacctct aggaatgacg 550 tcatcgtgga gattatttag ggatgatgat tctgccatta taccttgtcg 600 cacaactgat cccgagactc ctgtaacctt acacaacagt gagggggtgg 650 tacctgcctc ctacgacagc agacagggct ttaatgggac cttcactgta 700 gggccctata tctgtgaggc caccgtcaaa ggaaagaagt tccagaccat 750 cccatttaat gtttatgctt taaaagcaac atcagagctg gatctagaaa 800 tggaagctct taaaaccgtg tataagtcag gggaaacgat tgtggtcacc 850 tgtgctgttt ttaacaatga ggtggttgac cttcaatgga cttaccctgg 900 ggcaaaggca agaagtgaaa tcacaatgct ggaagaaatc aaagtcccat 950 ccatcaaatt ggtgtacact ttgacggtcc ccgaggcc ac ggtgaaagac 1000 agtggagatt acgaatgtgc tgcccgccag gctaccaggg aggtcaaaga 1050 aatgaagaaa ctgtccatga gtcactattt attgaaatca gaaaggtttc 1100 aacccacctt cagccagttg gaagctgtca acctgcatga agtcaaacat 1150 tttgttgtag aggtgcgggc ctacccacct cccaggatat cctggctgaa 1200 aaacaatctg actctgattg aaaatctcac tgagatcacc actgatgtgg 1250 aaaagattca ggaaataagg tatcgaagca aattaaagct gatccgtgct 1300 aaggaagaag acagtggcca ttatactatt gtagctcaaa atgaagatgc 1350 tgtgaagagc tatacttttg aactgttaac tcaagttcct tcatccattc 1400 tggacttggt cgatgatcac catggctcaa ctgggggaca gacggtgagg 1450 tgcacagctg aaggcacgcc gcttcctgat attgagtgga tgatatgcaa 1500 agatattaag aaatgtaata atgaaacttc ctggactatt ttggccaaca 1550 atgtctcaaa catcatcacg gagatccact cccgagacag gagtaccgtg 1600 gagggccgtg tgactttcgc caaagtggag gagaccatcg ccgtgcgatg 1650 cctggctaag aatctccttg gagctgagaa ccgagagctg aagctggtgg 1700 ctcccaccct gcgttctgaa ctcacggtgg ctgctgcagt cctggtgctg 1750 ttggtgattg tgatcatctc acttattgtc ctggttgtca tttggaaaca 1800 gaaa ccgagg tatgaaattc gctggagggt cattgaatca atcagcccag 1850 atggacatga atatatttat gtggacccga tgcagctgcc ttatgactca 1900 agatgggagt ttccaagaga tggactagtg cttggtcggg tcttggggtc 1950 tggagcgttt gggaaggtgg ttgaaggaac agcctatgga ttaagccggt 2000 cccaacctgt catgaaagtt gcagtgaaga tgctaaaacc cacggccaga 2050 tccagtgaaa aacaagctct catgtctgaa ctgaagataa tgactcacct 2100 ggggccacat ttgaacattg taaacttgct gggagcctgc accaagtcag 2150 gccccattta catcatcaca gagtattgct tctatggaga tttggtcaac 2200 agaataggga tatttgcata tagcttcctg agccaccacc cagagaagcc 2250 aaagaaagag ctggatatct ttggattgaa ccctgctgat gaaagcacac 2300 ggagctatgt tattttatct tttgaaaaca atggtgacta catggacatg 2350 aagcaggctg atactacaca gtatgtcccc atgctagaaa ggaaagaggt 2400 ttctaaatat tccgacatcc agagatcact ctatgatcgt ccagcctcat 2450 atctatgtta ataagaagaa gactcagaag tcaaaaacct cctttcagat 2500 gataactcag aaggccttac tttattggat ttgttgagct tcacctatca 2550 agttgcccga ggaatggagt ttttggcttc aaaaaattgt gtccaccgtg 2600 atctggctgc tcgcaacgtc ctcctg GCAC aaggaaaaat tgtgaagatc 2650 tgtgactttg gcctggccag agacatcatg catgattcga actatgtgtc 2700 gaaaggcagt acctttctgc ccgtgaagtg gatggctcct gagagcatct 2750 ttgacaacct ctacaccaca ctgagtgatg tctggtctta tggcattctg 2800 ctctgggaga tcttttccct tggtggcacc ccttaccccg gcatgatggt 2850 ggattctact ttctacaata agatcaagag tgggtaccgg atggccaagc 2900 taccagtgaa ctgaccacgc gtctacgaga tcatggtgaa atgctggaac 2950 agtgagccgg agaagagacc ctccttttac cacctgagtg agattgtgga 3000 gaatctgctg cctggacaat ataaaaagag ttatgaaaaa attcacctgg 3050 acttcctgaa gagtgaccat cctgctgtgg cacgcatgcg tgtggactca 3100 gacaatgcat acattggtgt cacctacaaa aacgaggaag acaagctgaa 3150 ggactgggag ggtggtctgg atgagcagag actgagcgct gacagtggct 3200 acatcattcc tctgcctgac attgaccctg tccctgagga ggaggacctg 3250 ggcaagagga acagacacag ctcgcagacc gtgccattga tctgaagaga 3300 agcagttcca gacgggttcc ccttcatcaa gagagaggac gagaccattg 3350 aagacatcga catgatggat gacatcggca tagactcttc agacctggtg 3400 gaagacagct tcctgtaact ggcggattcg aggggttcct tccacttc tg 3450 gggccacctc tggatcccgt tcagaaaacc actttattgc aatgcagagg 3500 ttgagaggag gacttggttg atgtttaaag agaagttccc agccaagggc 3550 ctcggggagc gttctaaata tgaatgaatg ggatattttg aaatgaactt 3600 tgtcagtgtt gcctcttgca atgcctcagt agcatctcag tggtgtgtga 3650 tagatggata agtttggaga agggaataat aggccacaga aggtgaactt 3700 tgtgcttcaa ggacattggt gagagtccaa cagacacaat ttatactgcg 3750 agcattgtaa acagaacttc ttatgtaaat aactctaacc aaggctgtgt 3800 ttagattgta ttaactatct tctttggact tctgaagaga ccactcaatc 3850 catccatgta cttccctctt gaaacctgat gtcagctgct gttgaacttt 3900 ttaaagaagt gcatgaaaaa ccatttttga accttaaaag gtactggtac 3950 tatagcattt tgctatcttt tttagtgtta aagagataaa gaataataat 4000 taaccaacct tgtttaatag atttgggtca tgacaactca tttagaagcc 4050 ttttcatatt gtaatctatg tttataatac tactactgtt atcagtaatg 4100 ctaaatgtgt aataatgtaa catgatttcc ctccagagaa agcacaattt 4150 aaaacaatcc ttactaagta ggtgatgagt ttgacagttt ttgacattta 4200 tattaaataa catgtttctc tataaagtat ggtaatagct ttagtgaatt 4250 gagca aaatttagtt tagag aacaaagtaa aagtagtgtt gtccaggaag 4300 tcagaatttt taactgtact gaataggttc cccaatccat cgtattaaaa 4350 tgccctctga aacaattaac ttagaaacaa aataatggga acaaaactct 4400 aagttctcaa taagtcctaa tgtagaggca taaacctgtg ctgaacataa 4450 atattaccca cttctcatgt atggaaaata taatgatcag caaaaagact 4500 ggatttgcag aagttttttt tttttttttc ttcatgcctg atgaaagctt 4550 tggcgacccc aatatatgta ttttttgaat ctatgaacct gaaaagggtc 4600 agaaggatgc ccagacatca gcctccttct ttcacccctt accccaaaga 4650 gaaagagttt gaaactcgag accataaaga tattctttag tggaggctgg 4700 atgtgcatta gcctggatcc tcagttctca aatgtgtgtg gcagccagga 4750 tgactagatc ctgggtttcc ttctgaagta atccttgaga tgaagtctga 4800 gggaaaccag agtctgtatt tttctaaact ccctggctgt tctgatcggc 4850 cagttttcgg aaacactgac ttaggtttca atgggaaaca ggaagttgcc aataatttga 4900 actttggaac agggttggca ttcaaccacg caggaagcct actatttaaa 4950 tccttggctt caggttagtg acatttaatg ccatctagct 5000 agcaattgcg accttaattt aactttccag tcttagctga ggctgagaaa 5050 ggttttgaca gctaaagttt aagtaaa ggttttccaa gat gctacttccc 5100 actgtatggg ggagattgaa ctttccccgt ctcccgtctt ctgcctccca 5150 ctccataccc cgccaaggaa aggcatgtac aaaaattatg caattcagtg 5200 ttccaagtct ctgtgtaacc agctcagtgt tttggtggaa aaaacatttt 5250 aagttttact gataatttga ggttagatgg gaggatgaat tgtcacatct 5300 atccacactg tcaaacaggt tggtgtgggt tcattggcat tctttgcaat 5350 actgcttaat tgctgatacc atatgaatga aacatgggct gtgattactg 5400 gctatcggca caatcactgt gatgatgctt tggaagatgc agaagcaata 5450 ataaagtact tgactaccta ctggtgtaat ctcaatgcaa gccccaactt 5500 ctttttcata tcttatccaa gtaagtgcga agactgagcc agattggcca 5550 attaaaaacg aaaacctgac taggttctgt agagccaatt agacttgaaa 5600 tacgtttgtg tttctagaat cacagctcaa gcattctgtt tatcgctcac 5650 tctcccttgt acagccttat tttgttggtg ctttgcattt tgatattgct 5700 catgacatca gtgagccttg tgaggccgga tgaaacttct cagtccagca 5750 gtttccagtc ctaacaaatg ctcccacctg aatttgtata tgactgcatt 5800 tgtgtgtgtg tgtgtgtttt cagcaaattc cagatttgtt tccttttggc 5850 gtctccagaa ctcctgcaaa gaaaatttgc caatctttcc tactttctat 5900 tttt atgatg acaatcaaag ccggcctgag aaacactatt tgtgactttt 5950 taaacgatta gtgatgtcct taaaatgtgg tctgccaatc tgtacaaaat 6000 ggtcctattt ttgtgaagag ggacataaga taaaatgatg ttatacatca 6050 atatgtatat atgtatttct atatagactt ggagaatact gccaaaacat 6100 ttatgacaag ctgtatcact gccttcgttt atattttttt aactgtgata 6150 atccccacag gcacattaac tgttgcactt ttgaatgtcc aaaatttata 6200 ttttagaaat aagatactta aataaaaaga catgttccca aaacaatggt 6250 tgtgagaaaa gtggtgaatg actaacttga tagggtctac caatacaaaa 6300 tgtattacga atgcccctgt tcatgttttt gttttaaaac gtgtaaatga 6350 agatctttat atttcaataa atgatatata atttaaagtt 6390

<210> 14 <210> 14

<211> 5711 <211> 5711

<212> ADN <212> DNA

<213> Homo sapiens <213> Homo sapiens

<400> 14<400> 14

ctcctgaggc tgccagcagc cagcagtgac tgcccgccct atctgggacc 50 caggatcgct ctgtgagcaa cttggagcca gagaggagat caacaaggag 100 gaggagagag ccggcccctc agccctgctg cccagcagca gcctgtgctc 150 gccctgccca acgcagacag ccagacccag ggcggcccct ctggcggctc 200 tgctcctccc gaaggatgct tggggagtga ggcgaagctg ggccgctcct 250 ctcccctaca gcagccccct tcctccatcc ctctgttctc ctgagccttc 300 aggagcctgc accagtcctg cctgtccttc tactcagctg ttacccactc 350 tgggaccagc agtctttctg ataactggga gagggcagta aggaggactt 400 cctggagggg gtgactgtcc agagcctgga actgtgccca caccagaagc 450 catcagcagc aaggacacca tgcggcttcc gggtgcgatg ccagctctgg 500 ccctcaaagg cgagctgctg ttgctgtctc tcctgttact tctggaacca 550 cagatctctc agggcctggt cgtcacaccc ccggggccag agcttgtcct 600 caatgtctcc agcaccttcg ttctgacctg ctcgggttca gctccggtgg 650 tgtgggaacg gatgtcccag gagcccccac aggaaatggc caaggcccag 700 gatggcacct tctccagcgt gctcacactg accaacctca ctgggctaga 750 cacgggagaa tacttttgca cccacaatga ctcccgtgga ctggagaccg 800 atgagcggaa acggctctac atctttgtgc cagatcccac cgtgggcttc 850 ctccctaatg atgccgagga actattcatc tttctcacgg aaataactga 900 gatcaccatt ccatgccgag taacagaccc acagctggtg gtgacactgc 950 acgagaagaa aggggacgtt gcactgcctg tcccctatga tcaccaacgt 1000 ggcttttctg gtatctttga ggacagaagc tacatctgca aaaccaccat 1050 tggggacagg gaggtggatt ctgatgccta ctatgtctac agactccagg 1100 tgtcatccat caacgtctct gtgaacgcag tgcagactgt ggtccgccag 1150 ggtgagaaca tcaccctcat gtgcattgtg atcgggaatg aggtggtcaa 1200 cttcgagtgg acataccccc gcaaagaaag tgggcggctg gtggagccgg 1250 tgactgactt cctcttggat atgccttacc acatccgctc catcctgcac 1300 atccccagtg ccgagttaga agactcgggg acctacacct gcaatgtgac 1350 ggagagtgtg aatgaccatc aggatgaaaa ggccatcaac atcaccgtgg 1400 ttgagagcgg ctacgtgcgg ctcctgggag aggtgggcac actacaattt 1450 gctgagctgc atcggagccg gacactgcag gtagtgttcg aggcctaccc 1500 accgcccact gtcctgtggt tcaaagacaa ccgcaccctg ggcgactcca 1550 gcgctggcga aatcgccctg tccacgcgca acgtgtcgga gacccggtat 1600 gtgtcagagc tgacactggt tcgcgtgaag gtggcagagg ctggccacta 1650 caccatgcgg gccttccatg aggatgctga ggtccagctc tccttccagc 1700 tacagatcaa tgtccctgtc cgagtgctgg agctaagtga gagccaccct 1750 gacagtgggg aacagacagt ccgctgtcgt ggccggggca tgccccagcc 1800 gaacatcatc tggtctgcct gcagagacct caaaaggtgt ccacgtgagc 1850 tgccgcccac gctgctgggg aacagttccg aagaggagag ccagctggag 1900 actaacgtga cgtactggga ggaggagcag gagtttgagg tggtgagcac 1950 actgcgtctg cagcacgtgg atcggccact gtcggtgcgc tgcacgctgc 2000 gcaacgctgt gggccaggac acgcaggagg tcatcgtggt gccacactcc 2050 ttgcccttta aggtggtggt gatctcagcc atcctggccc tggtggtgct 2100 caccatcatc tcccttatca tcctcatcat gctttggcag aagaagccac 2150 gttacgagat ccgatggaag gtgattgagt ctgtgagctc tgacggccat 2200 gagtacatct acgtggaccc catgcagctg ccctatgact ccacgtggga 2250 gctgccgcgg gaccagcttg tgctgggacg caccctcggc tctggggcct 2300 ttgggcaggt ggtggaggcc acggctcatg gcctgagcca ttctcaggcc 2350 acgatgaaag tggccgtcaa gatgcttaaa tccacagccc gcagcagtga 2400 gaagcaagcc cttatgtcgg agctgaagat catgagtcac cttgggcccc 2450 acctgaacgt ggtcaacctg ttgggggcct gcaccaaagg aggacccatc 2500 tatatcatca ctgagtactg ccgctacgga gacctggtgg actacctgca 2550 ccgcaacaaa cacaccttcc tgcagcacca ctccgacaag cgccgcccgc 2600 ccagcgcgga gctctacagc aatgctctgc ccgttgggct ccccctgccc 2650 agccatgtgt ccttgaccgg ggagagcgac ggtggctaca tggacatgag 2700 caaggacgag tcggtggact atgtgcccat gctggacatg aaaggagacg 2750 tcaaatatgc agacatcgag tcctccaact acatggcccc ttacgataac 2800 tacgttccct ctgcccctga gaggacctgc cgagcaactt tgatcaacga 2850 gtctccagtg ctaagctaca tggacctcgt gggcttcagc taccaggtgg 2900 ccaatggcat ggagtttctg gcctccaaga actgcgtcca cagagacctg 2950 gcggctagga acgtgctcat ctgtgaaggc aagctggtca agatctgtga 3000 ctttggcctg gctcgagaca tcatgcggga ctcgaattac atctccaaag 3050 gcagcacctt tttgccttta aagtggatgg ctccggagag catcttcaac 3100 agcctctaca ccaccctgag cgacgtgtgg tccttcggga tcctgctctg 3150 ggagatcttc accttgggtg gcacccctta cccagagctg cccatgaacg 3200 agcagttcta caatgccatc aaacggggtt accgcatggc ccagcctgcc 3250 catgcctccg acgagatcta tgagatcatg cagaagtgct gggaagagaa 3300 gtttgagatt cggcccccct tctcccagct ggtgctgctt ctcgagagac 3350 tgttgggcga aggttacaaa aagaagtacc agcaggtgga tgaggagttt 3400 ctgaggagtg accacccagc catccttcgg tcccaggccc gcttgcctgg 3450 gttccatggc ctccgatctc ccctggacac cagctccgtc ctctatactg 3500 ccgtgcagcc caatgagggt gacaacgact atatcatccc cctgcctgac 3550 cccaaacccg aggttgctga cgagggccca ctggagggtt cccccagcct 3600 agccagctcc accctgaatg aagtcaacac ctcctcaacc atctcctgtg 3650 acagccccct ggagccccag gacgaaccag agccagagcc ccagcttgag 3700 ctccaggtgg agccggagcc agagctggaa cagttgccgg attcggggtg 3750 ccctgcgcct cgggcggaag cagaggatag cttcctgtag ggggctggcc 3800 cctaccctgc cctgcctgaa gctccccccc tgccagcacc cagcatctcc 3850 tggcctggcc tgaccgggct tcctgtcagc caggctgccc ttatcagctg 3900 tccccttctg gaagctttct gctcctgacg tgttgtgccc caaaccctgg 3950 ggctggctta ggaggcaaga aaactgcagg ggccgtgacc agccctctgc 4000 ctccagggag gccaactgac tctgagccag ggttccccca gggaactcag 4050 ttttcccata tgtaaaatgg gaaagttagg cttgatgacc cagaatctag 4100 gattctctcc ctggctgaca ggtggggaga ccgaatccct ccctgggaag 4150 attcttggag ttactgaggt ggtaaattaa cttttttctg ttcagccagc 4200 tacccctcaa ggaatcatag ctctctcctc gcacttttat ccacccagga 4250 gctagggaag agaccctagc ctccctggct gctggctgag ctagggccta 4300 gccttgagca gtgttgcctc atccagaaga aagccagtct cctccctatg 4350 atgccagtcc ctgcgttccc tggcccgagc tggtctgggg ccattaggca 4400 gcctaattaa tgctggaggc tgagccaagt acaggacacc cccagcctgc 4450 agcccttgcc cagggcactt ggagcacacg cagccatagc aagtgcctgt 4500 gtccctgtcc ttcaggccca tcagtcctgg ggctttttct ttatcaccct 4550 cagtcttaat ccatccacca gagtctagaa ggccagacgg gccccgcatc 4600 tgtgatgaga atgtaaatgt gccagtgtgg agtggccacg tgtgtgtgcc 4650 agtatatggc cctggctctg cattggacct gctatgaggc tttggaggaa 4700 tccctcaccc tctctgggcc tcagtttccc cttcaaaaaa tgaataagtc 4750 ggacttatta actctgagtg ccttgccagc actaacattc tagagtattc 4800 caggtggttg cacatttgtc cagatgaagc aaggccatat accctaaact 4850 tccatcctgg gggtcagctg ggctcctggg agattccaga tcacacatca 4900 cactctgggg actcaggaac catgcccctt ccccaggccc ccagcaagtc 4950 tcaagaacac agctgcacag gccttgactt agagtgacag ccggtgtcct 5000 ggaaagcccc cagcagctgc cccagggaca tgggaagacc acgggacctc 5050 tttcactacc cacgatgacc tccgggggta tcctgggcaa aagggacaaa 5100 gagggcaaat gagatcacct cctgcagccc accactccag cacctgtgcc 5150 gaggtctgcg tcgaagacag aatggacagt gaggacagtt atgtcttgta 5200 aaagacaaga agcttcagat gggtacccca agaaggatgt gagaggtggg 5250 cgctttggag gtttgcccct cacccaccag ctgccccatc cctgaggcag 5300 cgctccatgg gggtatggtt ttgtcactgc ccagacctag cagtgacatc 5350 tcattgtccc cagcccagtg ggcattggag gtgccagggg agtcagggtt 5400 gtagccaaga cgcccccgca cggggagggt tgggaagggg gtgcaggaag 5450 ctcaacccct ctgggcacca accctgcatt gcaggttggc accttacttc 5500 cctgggatcc ccagagttgg tccaaggagg gagagtgggt tctcaatacg 5550 gtaccaaaga tataatcacc taggtttaca aatattttta ggactcacgt 5600 taactcacat ttatacagca gaaatgctat tttgtatgct gttgagtttt 5650 tctatctgtg tacttttttt taagggaaag attttaatat taaacctggt 5700 gcttctcact c 5711 ctcctgaggc tgccagcagc cagcagtgac tgcccgccct atctgggacc 50 caggatcgct ctgtgagcaa cttggagcca gagaggagat caacaaggag 100 gaggagagag ccggcccctc agccctgctg cccagcagca gcctgtgctc 150 gccctgccca acgcagacag ccagacccag ggcggcccct ctggcggctc 200 tgctcctccc gaaggatgct tggggagtga ggcgaagctg ggccgctcct 250 ctcccctaca gcagccccct tcctccatcc ctctgttctc ctgagccttc 300 aggagcctgc accagtcctg cctgtccttc tactcagctg ttacccactc 350 tgggaccagc agtctttctg ataactggga gagggcagta aggaggactt 400 cctggagggg gtgactgtcc agagcctgga actgtgccca caccagaagc 450 aaggacacca catcagcagc tgcggcttcc gggtgcgatg ccagctctgg 500 ccctcaaagg cgagctgctg ttgctgtctc tcctgttact tctggaacca 550 cagatctctc agggcctggt cgtcacaccc ccggggccag agcttgtcct 600 caatgtctcc agcaccttcg ttctgacctg ctcgggttca gctccggtgg 650 tgtgggaacg gatgtcccag gagcccccac aggaaatggc caaggcccag 700 gatggcacct tctccagcgt gctcacactg accaacctca ctgggctaga 750 cacgggagaa tacttttgca cccacaatga ctcccgtgga ctggagaccg 800 atgagcggaa acggctctac atctttgtgc cagatccc ac cgtgggcttc 850 ctccctaatg atgccgagga actattcatc tttctcacgg aaataactga 900 gatcaccatt ccatgccgag taacagaccc acagctggtg gtgacactgc 950 acgagaagaa aggggacgtt gcactgcctg tcccctatga tcaccaacgt 1000 ggcttttctg gtatctttga ggacagaagc tacatctgca aaaccaccat 1050 tggggacagg gaggtggatt ctgatgccta ctatgtctac agactccagg 1100 tgtcatccat caacgtctct gtgaacgcag tgcagactgt ggtccgccag 1150 ggtgagaaca tcaccctcat gtgcattgtg atcgggaatg aggtggtcaa 1200 cttcgagtgg acataccccc gcaaagaaag tgggcggctg gtggagccgg 1250 tgactgactt cctcttggat atgccttacc acatccgctc catcctgcac 1300 atccccagtg ccgagttaga agactcgggg acctacacct gcaatgtgac 1350 ggagagtgtg aatgaccatc aggatgaaaa ggccatcaac atcaccgtgg 1400 ttgagagcgg ctacgtgcgg ctcctgggag aggtgggcac actacaattt 1450 gctgagctgc atcggagccg gacactgcag gtagtgttcg aggcctaccc 1500 accgcccact gtcctgtggt tcaaagacaa ccgcaccctg ggcgactcca 1550 gcgctggcga aatcgccctg tccacgcgca acgtgtcgga gacccggtat 1600 gtgtcagagc tgacactggt tcgcgtgaag gtggcagagg ctggccacta 1650 caccatg CGG gccttccatg aggatgctga ggtccagctc tccttccagc 1700 tacagatcaa tgtccctgtc cgagtgctgg agctaagtga gagccaccct 1750 gacagtgggg aacagacagt ccgctgtcgt ggccggggca tgccccagcc 1800 gaacatcatc tggtctgcct gcagagacct caaaaggtgt ccacgtgagc 1850 tgccgcccac gctgctgggg aacagttccg aagaggagag ccagctggag 1900 cgtactggga actaacgtga ggaggagcag gagtttgagg tggtgagcac 1950 actgcgtctg cagcacgtgg atcggccact gtcggtgcgc tgcacgctgc 2000 gcaacgctgt gggccaggac acgcaggagg tcatcgtggt gccacactcc 2050 ttgcccttta aggtggtggt gatctcagcc atcctggccc tggtggtgct 2100 tcccttatca caccatcatc tcctcatcat gctttggcag aagaagccac 2150 gttacgagat ccgatggaag gtgattgagt ctgtgagctc tgacggccat 2200 gagtacatct acgtggaccc catgcagctg ccctatgact ccacgtggga 2250 gctgccgcgg gaccagcttg tgctgggacg caccctcggc tctggggcct 2300 ttgggcaggt ggtggaggcc acggctcatg gcctgagcca ttctcaggcc 2350 tggccgtcaa acgatgaaag tccacagccc gatgcttaaa gcagcagtga 2400 gaagcaagcc cttatgtcgg agctgaagat catgagtcac cttgggcccc 2450 acctgaacgt ggtcaacctg ttgggggcct gcaccaaagg aggacccatc 2500 tatatcatca ctgagtactg ccgctacgga gacctggtgg actacctgca 2550 ccgcaacaaa cacaccttcc tgcagcacca ctccgacaag cgccgcccgc 2600 ccagcgcgga gctctacagc aatgctctgc ccgttgggct ccccctgccc 2650 agccatgtgt ccttgaccgg ggagagcgac ggtggctaca tggacatgag 2700 caaggacgag tcggtggact atgtgcccat gctggacatg aaaggagacg 2750 tcaaatatgc agacatcgag tcctccaact acatggcccc ttacgataac 2800 tacgttccct ctgcccctga gaggacctgc cgagcaactt tgatcaacga 2850 gtctccagtg ctaagctaca tggacctcgt gggcttcagc taccaggtgg 2900 ccaatggcat ggagtttctg gcctccaaga actgcgtcca cagagacctg 2950 acgtgctcat gcggctagga ctgtgaaggc aagctggtca agatctgtga 3000 gctcgagaca ctttggcctg tcatgcggga ctcgaattac atctccaaag 3050 gcagcacctt tttgccttta aagtggatgg ctccggagag catcttcaac 3100 agcctctaca ccaccctgag cgacgtgtgg tccttcggga tcctgctctg 3150 ggagatcttc accttgggtg gcacccctta cccagagctg cccatgaacg 3200 agcagttcta caatgccatc aaacggggtt accgcatggc ccagcctgcc 3250 catgcctccg acgagatcta tgagatcatg cagaagtgct gggaagagaa 33 00 gtttgagatt cggcccccct tctcccagct ggtgctgctt ctcgagagac 3350 aggttacaaa tgttgggcga aagaagtacc agcaggtgga tgaggagttt 3400 ctgaggagtg accacccagc catccttcgg tcccaggccc gcttgcctgg 3450 gttccatggc ctccgatctc ccctggacac cagctccgtc ctctatactg 3500 ccgtgcagcc caatgagggt gacaacgact atatcatccc cctgcctgac 3550 aggttgctga cccaaacccg cgagggccca ctggagggtt cccccagcct 3600 agccagctcc accctgaatg aagtcaacac ctcctcaacc atctcctgtg 3650 acagccccct ggagccccag gacgaaccag agccagagcc ccagcttgag 3700 ctccaggtgg agccggagcc agagctggaa cagttgccgg attcggggtg 3750 ccctgcgcct cgggcggaag cagaggatag cttcctgtag ggggctggcc 3800 cctaccctgc cctgcctgaa gctccccccc tgccagcacc cagcatctcc 3850 tggcctggcc tgaccgggct tcctgtcagc caggctgccc ttatcagctg 3900 tccccttctg gaagctttct gctcctgacg tgttgtgccc caaaccctgg 3950 ggaggcaaga ggctggctta aaactgcagg ggccgtgacc agccctctgc 4000 ctccagggag gccaactgac tctgagccag ggttccccca gggaactcag 4050 ttttcccata tgtaaaatgg gaaagttagg cttgatgacc cagaatctag 4100 ctggctgaca gattctctcc ggtggggaga ccgaatccct ccctgggaag 4150 attcttggag ttactgaggt ggtaaattaa cttttttctg ttcagccagc 4200 tacccctcaa ggaatcatag ctctctcctc gcacttttat ccacccagga 4250 gctagggaag agaccctagc ctccctggct gctggctgag ctagggccta 4300 gccttgagca gtgttgcctc atccagaaga aagccagtct cctccctatg 4350 atgccagtcc ctgcgttccc tggcccgagc tggtctgggg ccattaggca 4400 gcctaattaa tgctggaggc tgagccaagt acaggacacc cccagcctgc 4450 agcccttgcc cagggcactt ggagcacacg cagccatagc aagtgcctgt 4500 gtccctgtcc ttcaggccca tcagtcctgg ggctttttct ttatcaccct 4550 ccatccacca cagtcttaat gagtctagaa ggccagacgg gccccgcatc 4600 tgtgatgaga atgtaaatgt gccagtgtgg agtggccacg tgtgtgtgcc 4650 agtatatggc cctggctctg cattggacct gctatgaggc tttggaggaa 4700 tccctcaccc tctctgggcc tcagtttccc cttcaaaaaa tgaataagtc 4750 ggacttatta actctgagtg ccttgccagc actaacattc tagagtattc 4800 caggtggttg cacatttgtc cagatgaagc aaggccatat accctaaact 4850 tccatcctgg gggtcagctg ggctcctggg tcacacatca agattccaga 4900 cactctgggg actcaggaac catgcccctt ccccaggccc c cagcaagtc 4950 tcaagaacac agctgcacag gccttgactt agagtgacag ccggtgtcct 5000 ggaaagcccc cagcagctgc cccagggaca tgggaagacc acgggacctc 5050 tttcactacc cacgatgacc tcctgggcaa tccgggggta aagggacaaa 5100 gagggcaaat gagatcacct cctgcagccc accactccag cacctgtgcc 5150 gaggtctgcg tcgaagacag aatggacagt gaggacagtt atgtcttgta 5200 aaagacaaga agcttcagat gggtacccca agaaggatgt gagaggtggg 5250 cgctttggag gtttgcccct cacccaccag ctgccccatc cctgaggcag 5300 cgctccatgg gggtatggtt ttgtcactgc ccagacctag cagtgacatc 5350 tcattgtccc cagcccagtg ggcattggag gtgccagggg agtcagggtt 5400 cgcccccgca gtagccaaga cggggagggt tgggaagggg gtgcaggaag 5450 ctgggcacca ctcaacccct accctgcatt gcaggttggc accttacttc 5500 cctgggatcc ccagagttgg tccaaggagg gagagtgggt tctcaatacg 5550 gtaccaaaga tataatcacc taggtttaca aatattttta ggactcacgt 5600 taactcacat ttatacagca gaaatgctat tttgtatgct gttgagtttt 5650 tctatctgtg tacttttttt taagggaaag attttaatat taaacctggt gcttctcact 5700 c 5711

<210> 15 <210> 15

<211> 2115 <211> 2115

<212> ADN <212> DNA

<213> Homo sapiens <213> Homo sapiens

<400> 15 <400> 15

atgagtgctg cagtgactgc agggaagctg gcacgggcac cggccgaccc 50 atgagtgctg cagtgactgc agggaagctg gcacgggcac cggccgaccc 50

tgggaaagcc ggggtccccg gagttgcagc tcccggagct ccggcggcgg 100 tgggaaagcc ggggtccccg gagttgcagc tcccggagct ccggcggcgg 100

ctccaccggc gaaagagatc ccggaggtcc tagtggaccc acgcagccgg 150 ctccaccggc gaaagagatc ccggaggtcc tagtggaccc acgcagccgg 150

cggcgctatg tgcggggccg ctttttgggc aagggcggct ttgccaagtg 200 cggcgctatg tgcggggccg ctttttgggc aagggcggct ttgccaagtg 200

cttcgagatc tcggacgcgg acaccaagga ggtgttcgcg ggcaagattg 250 cttcgagatc tcggacgcgg acaccaagga ggtgttcgcg ggcaagattg 250

tgcctaagtc tctgctgctc aagccgcacc agagggagaa gatgtccatg 300 tgcctaagtc tctgctgctc aagccgcacc agagggagaa gatgtccatg 300

gaaatatcca ttcaccgcag cctcgcccac cagcacgtcg taggattcca 350 gaaatatcca ttcaccgcag cctcgcccac cagcacgtcg taggattcca 350

cggctttttc gaggacaacg acttcgtgtt cgtggtgttg gagctctgcc 400 cggctttttc gaggacaacg acttcgtgtt cgtggtgttg gagctctgcc 400

gccggaggtc tctcctggag ctgcacaaga ggaggaaagc cctgactgag 450 gccggaggtc tctcctggag ctgcacaaga ggaggaaagc cctgactgag 450

cctgaggccc gatactacct acggcaaatt gtgcttggct gccagtacct 500 cctgaggccc gatactacct acggcaaatt gtgcttggct gccagtacct 500

gcaccgaaac cgagttattc atcgagacct caagctgggc aaccttttcc 550 gcaccgaaac cgagttattc atcgagacct caagctgggc aaccttttcc 550

tgaatgaaga tctggaggtg aaaatagggg attttggact ggcaaccaaa 600 tgaatgaaga tctggaggtg aaaatagggg attttggact ggcaaccaaa 600

gtcgaatatg acggggagag gaagaagacc ctgtgtggga ctcctaatta 650 gtcgaatatg acggggagag gaagaagacc ctgtgtggga ctcctaatta 650

catagctccc gaggtgctga gcaagaaagg gcacagtttc gaggtggatg 700 catagctccc gaggtgctga gcaagaaagg gcacagtttc gaggtggatg 700

tgtggtccat tgggtgtatc atgtatacct tgttagtggg caaaccacct 750 tgtggtccat tgggtgtatc atgtatacct tgttagtggg caaaccacct 750

tttgagactt cttgcctaaa agagacctac ctccggatca agaagaatga 800 tttgagactt cttgcctaaa agagacctac ctccggatca agaagaatga 800

atacagtatt cccaagcaca tcaaccccgt ggccgcctcc ctcatccaga 850 atacagtatt cccaagcaca tcaaccccgt ggccgcctcc ctcatccaga 850

agatgcttca gacagatccc actgcccgcc caaccattaa cgagctgctt 900 agatgcttca gacagatccc actgcccgcc caaccattaa cgagctgctt 900

aatgacgagt tctttacttc tggctatatc cctgcccgtc tccccatcac 950 aatgacgagt tctttacttc tggctatatc cctgcccgtc tccccatcac 950

ctgcctgacc attccaccaa ggttttcgat tgctcccagc agcctggacc 1000 ctgcctgacc attccaccaa ggttttcgat tgctcccagc agcctggacc 1000

ccagcaaccg gaagcccctc acagtcctca ataaaggctt ggagaacccc 1050 ccagcaaccg gaagcccctc acagtcctca ataaaggctt ggagaacccc 1050

ctgcctgagc gtccccggga aaaagaagaa ccagtggttc gagagacagg 1100 ctgcctgagc gtccccggga aaaagaagaa ccagtggttc gagagacagg 1100

tgaggtggtc gactgccacc tcagtgacat gctgcagcag ctgcacagtg 1150 tgaggtggtc gactgccacc tcagtgacat gctgcagcag ctgcacagtg 1150

tcaatgcctc caagccctcg gagcgtgggc tggtcaggca agaggaggct 1200 tcaatgcctc caagccctcg gagcgtgggc tggtcaggca agaggaggct 1200

gaggatcctg cctgcatccc catcttctgg gtcagcaagt gggtggacta 1250 gaggatcctg cctgcatccc catcttctgg gtcagcaagt gggtggacta 1250

ttcggacaag tacggccttg ggtatcagct ctgtgataac agcgtggggg 1300 ttcggacaag tacggccttg ggtatcagct ctgtgataac agcgtggggg 1300

tgctcttcaa tgactcaaca cgcctcatcc tctacaatga tggtgacagc 1350 ctgcagtaca tagagcgtga cggcactgag tcctacctca ccgtgagttc 1400 ccatcccaac tccttgatga agaagatcac cctccttaaa tatttccgca 1450 attacatgag cgagcacttg ctgaaggcag gtgccaacat cacgccgcgc 1500 gaaggtgatg agctcgcccg gctgccctac ctacggacct ggttccgcac 1550 ccgcagcgcc atcatcctgc acctcagcaa cggcagcgtg cagatcaact 1600 tcttccagga tcacaccaag ctcatcttgt gcccactgat ggcagccgtg 1650 acctacatcg acgagaagcg ggacttccgc acataccgcc tgagtctcct 1700 ggaggagtac ggctgctgca aggagctggc cagccggctc cgctacgccc 1750 gcactatggt ggacaagctg ctgagctcac gctcggccag caaccgtctc 1800 aaggcctcct aatagctgcc ctcccctccg gactggtgcc ctcctcactc 1850 ccacctgcat ctggggccca tactggttgg ctcccgcggt gccatgtctg 1900 cagtgtgccc cccagccccg gtggctgggc agagctgcat catccttgca 1950 ggtgggggtt gctgtataag ttatttttgt acatgttcgg gtgtgggttc 2000 tacagccttg tccccctccc cctcaacccc accatatgaa ttgtacagaa 2050 tatttctatt gaattcggaa ctgtcctttc cttggcttta tgcacattaa 2100 acagatgtga atatt 2115 tgctcttcaa tgactcaaca cgcctcatcc tctacaatga tggtgacagc 1350 tagagcgtga ctgcagtaca cggcactgag tcctacctca ccgtgagttc 1400 tccttgatga ccatcccaac agaagatcac tatttccgca cctccttaaa 1450 attacatgag cgagcacttg ctgaaggcag gtgccaacat cacgccgcgc 1500 gaaggtgatg agctcgcccg gctgccctac ctacggacct ggttccgcac 1550 ccgcagcgcc atcatcctgc acctcagcaa cggcagcgtg cagatcaact 1600 tcttccagga tcacaccaag ctcatcttgt gcccactgat ggcagccgtg 1650 acctacatcg acgagaagcg ggacttccgc acataccgcc tgagtctcct 1700 ggctgctgca ggaggagtac aggagctggc cagccggctc cgctacgccc 1750 gcactatggt ggacaagctg ctgagctcac gctcggccag caaccgtctc 1800 aaggcctcct aatagctgcc ctcccctccg gactggtgcc ctcctcactc 1850 ccacctgcat ctggggccca tactggttgg ctcccgcggt gccatgtctg 1900 cagtgtgccc cccagccccg gtggctgggc agagctgcat catccttgca 1950 ggtgggggtt gctgtataag ttatttttgt acatgttcgg gtgtgggttc 2000 tacagccttg tccccctccc cctcaacccc accatatgaa ttgtacagaa 2050 tatttctatt gaattcggaa ctgtcctttc cttggcttta tgcacattaa 2100 acagatgtga atatt 2115

<210> 16 <210> 16

<211> 3236 <211> 3236

<212> ADN <212> DNA

<213> Homo sapiens <213> Homo sapiens

<400> 16 <400> 16

cgtggccctg tggcagccga gccatggttt ctaaactgag ccagctgcag 50 cgtggccctg tggcagccga gccatggttt ctaaactgag ccagctgcag 50

acggagctcc tggcggccct gctcgagtca gggctgagca aagaggcact 100 acggagctcc tggcggccct gctcgagtca gggctgagca aagaggcact 100

gatccaggca ctgggtgagc cggggcccta cctcctggct ggagaaggcc 150 gatccaggca ctgggtgagc cggggcccta cctcctggct ggagaaggcc 150

ccctggacaa gggggagtcc tgcggcggcg gtcgagggga gctggctgag 200 ccctggacaa gggggagtcc tgcggcggcg gtcgagggga gctggctgag 200

ctgcccaatg ggctggggga gactcggggc tccgaggacg agacggacga 250 ctgcccaatg ggctggggga gactcggggc tccgaggacg agacggacga 250

cgatggggaa gacttcacgc cacccatcct caaagagctg gagaacctca 300 cgatggggaa gacttcacgc cacccatcct caaagagctg gagaacctca 300

gccctgagga ggcggcccac cagaaagccg tggtggagac ccttctgcag 350 gccctgagga ggcggcccac cagaaagccg tggtggagac ccttctgcag 350

gaggacccgt ggcgtgtggc gaagatggtc aagtcctacc tgcagcagca 400 gaggacccgt ggcgtgtggc gaagatggtc aagtcctacc tgcagcagca 400

caacatccca cagcgggagg tggtcgatac cactggcctc aaccagtccc 450 caacatccca cagcgggagg tggtcgatac cactggcctc aaccagtccc 450

acctgtccca acacctcaac aagggcactc ccatgaagac gcagaagcgg 500 acctgtccca acacctcaac aagggcactc ccatgaagac gcagaagcgg 500

gccgccctgt acacctggta cgtccgcaag cagcgagagg tggcgcagca 550 gccgccctgt acacctggta cgtccgcaag cagcgagagg tggcgcagca 550

gttcacccat gcagggcagg gagggctgat tgaagagccc acaggtgatg 600 gttcacccat gcagggcagg gagggctgat tgaagagccc acaggtgatg 600

agctaccaac caagaagggg cggaggaacc gtttcaagtg gggcccagca 650 agctaccaac caagaagggg cggaggaacc gtttcaagtg gggcccagca 650

tcccagcaga tcctgttcca ggcctatgag aggcagaaga accctagcaa 700 tcccagcaga tcctgttcca ggcctatgag aggcagaaga accctagcaa 700

ggaggagcga gagacgctag tggaggagtg caatagggcg gaatgcatcc 750 agagaggggt gtccccatca caggcacagg ggctgggctc caacctcgtc 800 acggaggtgc gtgtctacaa ctggtttgcc aaccggcgca aagaagaagc 850 cttccggcac aagctggcca tggacacgta cagcgggccc cccccagggc 900 caggcccggg acctgcgctg cccgctcaca gctcccctgg cctgcctcca 950 cctgccctct cccccagtaa ggtccacggt gtgcgctatg gacagcctgc 1000 gaccagtgag actgcagaag taccctcaag cagcggcggt cccttagtga 1050 cagtgtctac acccctccac caagtgtccc ccacgggcct ggagcccagc 1100 cacagcctgc tgagtacaga agccaagctg gtctcagcag ctgggggccc 1150 cctcccccct gtcagcaccc tgacagcact gcacagcttg gagcagacat 1200 ccccaggcct caaccagcag ccccagaacc tcatcatggc ctcacttcct 1250 ggggtcatga ccatcgggcc tggtgagcct gcctccctgg gtcctacgtt 1300 caccaacaca ggtgcctcca ccctggtcat cggcctggcc tccacgcagg 1350 cacagagtgt gccggtcatc aacagcatgg gcagcagcct gaccaccctg 1400 cagcccgtcc agttctccca gccgctgcac ccctcctacc agcagccgct 1450 catgccacct gtgcagagcc atgtgaccca gagccccttc atggccacca 1500 tggctcagct gcagagcccc cacgccctct acagccacaa gcccgaggtg 1550 gcccagtaca cccacacggg cctgctcccg cagactatgc tcatcaccga 1600 caccaccaac ctgagcgccc tggccagcct cacgcccacc aagcaggtct 1650 tcacctcaga cactgaggcc tccagtgagt ccgggcttca cacgccggca 1700 tctcaggcca ccaccctcca cgtccccagc caggaccctg ccagcatcca 1750 gcacctgcag ccggcccacc ggctcagcgc cagccccaca gtgtcctcca 1800 gcagcctggt gctgtaccag agctcagact ccagcaatgg ccagagccac 1850 ctgctgccat ccaaccacag cgtcatcgag accttcatct ccacccagat 1900 ggcctcttcc tcccagtaac cacggcacct gggccctggg gcctgtactg 1950 cctgcttggg gggtgatgag ggcagcagcc agccctgcct ggaggacctg 2000 agcctgccga gcaaccgtgg cccttcctgg acagctgtgc ctcgctcccc 2050 actctgctct gatgcatcag aaagggaggg ctctgaggcg ccccaacccg 2100 tggaggctgc tcggggtgca caggaggggg tcgtggagag ctaggagcaa 2150 agcctgttca tggcagatgt aggagggact gtcgctgctt cgtgggatac 2200 agtcttctta cttggaactg aagggggcgg cctatgactt gggcaccccc 2250 agcctgggcc tatggagagc cctgggaccg ctacaccact ctggcagcca 2300 cacttctcag gacacaggcc tgtgtagctg tgacctgctg agctctgaga 2350 ggccctggat cagcgtggcc ttgttctgtc accaatgtac ccaccgggcc 2400 actccttcct gccccaactc cttccagcta gtgacccaca tgccatttgt 2450 actgacccca tcacctactc acacaggcat ttcctgggtg gctactctgt 2500 gccagagcct ggggctctaa cgcctgagcc cagggaggcc gaagctaaca 2550 gggaaggcag gcagggctct cctggcttcc catccccagc gattccctct 2600 cccaggcccc atgacctcca gctttcctgt atttgttccc aagagcatca 2650 tgcctctgag gccagcctgg cctcctgcct ctactgggaa ggctacttcg 2700 gggctgggaa gtcgtcctta ctcctgtggg agcctcgcaa cccgtgccaa 2750 gtccaggtcc tggtggggca gctcctctgt ctcgagcgcc ctgcagaccc 2800 tgcccttgtt tggggcagga gtagctgagc tcacaaggca gcaaggcccg 2850 agcagctgag cagggccggg gaactggcca agctgaggtg cccaggagaa 2900 gaaagaggtg accccagggc acaggagcta cctgtgtgga caggactaac 2950 actcagaagc ctgggggcct ggctggctga gggcagttcg cagccaccct 3000 gaggagtctg aggtcctgag cactgccagg agggacaaag gagcctgtga 3050 acccaggaca agcatggtcc cacatccctg ggcctgctgc tgagaacctg 3100 gccttcagtg taccgcgtct accctgggat tcaggaaaag gcctggggtg 3150 acccggcacc ccctgcagct tgtagccagc cggggcgagt ggcacgttta 3200 tttaactttt agtaaagtca aggagaaatg cggtgg 3236 ggaggagcga gagacgctag tggaggagtg caatagggcg gaatgcatcc 750 agagaggggt gtccccatca caggcacagg ggctgggctc caacctcgtc 800 gtgtctacaa acggaggtgc aaccggcgca ctggtttgcc aagaagaagc 850 aagctggcca cttccggcac tggacacgta cagcgggccc cccccagggc 900 caggcccggg acctgcgctg cccgctcaca gctcccctgg cctgcctcca 950 cctgccctct cccccagtaa ggtccacggt gtgcgctatg gacagcctgc 1000 gaccagtgag actgcagaag taccctcaag cagcggcggt cccttagtga 1050 cagtgtctac acccctccac caagtgtccc ccacgggcct ggagcccagc 1100 tgagtacaga cacagcctgc agccaagctg gtctcagcag ctgggggccc 1150 cctcccccct gtcagcaccc tgacagcact gcacagcttg gagcagacat 1200 ccccaggcct caaccagcag ccccagaacc tcatcatggc ctcacttcct 1250 ggggtcatga ccatcgggcc tggtgagcct gcctccctgg gtcctacgtt 1300 ggtgcctcca caccaacaca ccctggtcat cggcctggcc tccacgcagg 1350 cacagagtgt gccggtcatc aacagcatgg gcagcagcct gaccaccctg 1400 agttctccca cagcccgtcc gccgctgcac ccctcctacc agcagccgct 1450 catgccacct gtgcagagcc atgtgaccca atggccacca gagccccttc 1500 tggctcagct gcagagcccc cacgccct ct acagccacaa gcccgaggtg 1550 gcccagtaca cccacacggg cctgctcccg cagactatgc tcatcaccga 1600 caccaccaac ctgagcgccc tggccagcct cacgcccacc aagcaggtct 1650 cactgaggcc tcacctcaga ccgggcttca tccagtgagt cacgccggca 1700 ccaccctcca tctcaggcca cgtccccagc caggaccctg ccagcatcca 1750 gcacctgcag ccggcccacc ggctcagcgc gtgtcctcca cagccccaca 1800 gcagcctggt gctgtaccag agctcagact ccagcaatgg ccagagccac 1850 ctgctgccat ccaaccacag cgtcatcgag accttcatct ccacccagat 1900 ggcctcttcc tcccagtaac cacggcacct gggccctggg gcctgtactg 1950 cctgcttggg gggtgatgag ggcagcagcc agccctgcct ggaggacctg 2000 agcctgccga gcaaccgtgg cccttcctgg acagctgtgc ctcgctcccc 2050 actctgctct gatgcatcag aaagggaggg ctctgaggcg ccccaacccg 2100 tggaggctgc tcggggtgca caggaggggg tcgtggagag ctaggagcaa agcctgttca 2150 tggcagatgt aggagggact gtcgctgctt cgtgggatac 2200 agtcttctta cttggaactg aagggggcgg cctatgactt gggcaccccc 2250 agcctgggcc tatggagagc cctgggaccg ctacaccact ctggcagcca 2300 cacttctcag gacacaggcc tgtgtagctg tgacctgctg agctctgaga 2350 ggccctggat cagcgtggcc ttgttctgtc accaatgtac ccaccgggcc 2400 actccttcct gccccaactc cttccagcta gtgacccaca tgccatttgt 2450 actgacccca tcacctactc acacaggcat ttcctgggtg gctactctgt 2500 gccagagcct ggggctctaa cgcctgagcc cagggaggcc gaagctaaca 2550 gggaaggcag gcagggctct cctggcttcc catccccagc gattccctct 2600 atgacctcca cccaggcccc gctttcctgt atttgttccc aagagcatca 2650 tgcctctgag gccagcctgg cctcctgcct ctactgggaa ggctacttcg 2700 gggctgggaa gtcgtcctta ctcctgtggg agcctcgcaa cccgtgccaa 2750 gtccaggtcc tggtggggca gctcctctgt ctcgagcgcc ctgcagaccc 2800 tgcccttgtt tggggcagga gtagctgagc tcacaaggca gcaaggcccg 2850 agcagctgag cagggccggg gaactggcca agctgaggtg cccaggagaa 2900 gaaagaggtg accccagggc cctgtgtgga acaggagcta caggactaac 2950 actcagaagc ctgggggcct ggctggctga gggcagttcg cagccaccct 3000 gaggagtctg aggtcctgag cactgccagg agggacaaag gagcctgtga 3050 acccaggaca agcatggtcc cacatccctg ggcctgctgc tgagaacctg 3100 gccttcagtg taccgcgtct accctgggat tcaggaaaag gcctggggtg 3150 acccggcacc ccctgca gct tgtagccagc cggggcgagt ggcacgttta 3200 tttaactttt agtaaagtca aggagaaatg cggtgg 3236

<210> 17 <210> 17

<211> 2621 <211> 2621

<212> ADN <212> DNA

<213> Homo sapiens <213> Homo sapiens

<400> 17 <400> 17

acttgtcatg gcgactgtcc agctttgtgc caggagcctc gcaggggttg 50 acttgtcatg gcgactgtcc agctttgtgc caggagcctc gcaggggttg 50

atgggattgg ggttttcccc tcccatgtgc tcaagactgg cgctaaaagt 100 atgggattgg ggttttcccc tcccatgtgc tcaagactgg cgctaaaagt 100

tttgagcttc tcaaaagtct agagccaccg tccagggagc aggtagctgc 150 tttgagcttc tcaaaagtct agagccaccg tccagggagc aggtagctgc 150

tgggctccgg ggacactttg cgttcgggct gggagcgtgc tttccacgac 200 tgggctccgg ggacactttg cgttcgggct gggagcgtgc tttccacgac 200

ggtgacacgc ttccctggat tggcagccag actgccttcc gggtcactgc 250 ggtgacacgc ttccctggat tggcagccag actgccttcc gggtcactgc 250

catggaggag ccgcagtcag atcctagcgt cgagccccct ctgagtcagg 300 catggaggag ccgcagtcag atcctagcgt cgagccccct ctgagtcagg 300

aaacattttc agacctatgg aaactacttc ctgaaaacaa cgttctgtcc 350 aaacattttc agacctatgg aaactacttc ctgaaaacaa cgttctgtcc 350

cccttgccgt cccaagcaat ggatgatttg atgctgtccc cggacgatat 400 cccttgccgt cccaagcaat ggatgatttg atgctgtccc cggacgatat 400

tgaacaatgg ttcactgaag acccaggtcc agatgaagct cccagaatgc 450 tgaacaatgg ttcactgaag acccaggtcc agatgaagct cccagaatgc 450

cagaggctgc tccccccgtg gcccctgcac cagcagctcc tacaccggcg 500 cagaggctgc tccccccgtg gcccctgcac cagcagctcc tacaccggcg 500

gcccctgcac cagccccctc ctggcccctg tcatcttctg tcccttccca 550 gcccctgcac cagccccctc ctggcccctg tcatcttctg tcccttccca 550

gaaaacctac cagggcagct acggtttccg tctgggcttc ttgcattctg 600 gaaaacctac cagggcagct acggtttccg tctgggcttc ttgcattctg 600

ggacagccaa gtctgtgact tgcacgtact cccctgccct caacaagatg 650 ggacagccaa gtctgtgact tgcacgtact cccctgccct caacaagatg 650

ttttgccaac tggccaagac ctgccctgtg cagctgtggg ttgattccac 700 ttttgccaac tggccaagac ctgccctgtg cagctgtggg ttgattccac 700

acccccgccc ggcacccgcg tccgcgccat ggccatctac aagcagtcac 750 agcacatgac ggaggttgtg aggcgctgcc cccaccatga gcgctgctca 800 gatagcgatg gtctggcccc tcctcagcat cttatccgag tggaaggaaa 850 tttgcgtgtg gagtatttgg atgacagaaa cacttttcga catagtgtgg 900 tggtgcccta tgagccgcct gaggttggct ctgactgtac caccatccac 950 tacaactaca tgtgtaacag ttcctgcatg ggcggcatga accggaggcc 1000 catcctcacc atcatcacac tggaagactc cagtggtaat ctactgggac 1050 ggaacagctt tgaggtgcgt gtttgtgcct gtcctgggag agaccggcgc 1100 acagaggaag agaatctccg caagaaaggg gagcctcacc acgagctgcc 1150 cccagggagc actaagcgag cactgcccaa caacaccagc tcctctcccc 1200 agccaaagaa gaaaccactg gatggagaat atttcaccct tcagatccgt 1250 gggcgtgagc gcttcgagat gttccgagag ctgaatgagg ccttggaact 1300 caaggatgcc caggctggga aggagccagg ggggagcagg gctcactcca 1350 gccacctgaa gtccaaaaag ggtcagtcta cctcccgcca taaaaaactc 1400 atgttcaaga cagaagggcc tgactcagac tgacattctc cacttcttgt 1450 tccccactga cagcctccca cccccatctc tccctcccct gccattttgg 1500 gttttgggtc tttgaaccct tgcttgcaat aggtgtgcgt cagaagcacc 1550 caggacttcc atttgctttg tcccggggct ccactgaaca agttggcctg 1600 cactggtgtt ttgttgtggg gaggaggatg gggagtagga cataccagct 1650 tagattttaa ggtttttact gtgagggatg tttgggagat gtaagaaatg 1700 ttcttgcagt taagggttag tttacaatca gccacattct aggtaggggc 1750 ccacttcacc gtactaacca gggaagctgt ccctcactgt tgaattttct 1800 ctaacttcaa ggcccatatc tgtgaaatgc tggcatttgc acctacctca 1850 cagagtgcat tgtgagggtt aatgaaataa tgtacatctg gccttgaaac 1900 caccttttat tacatggggt ctagaacttg acccccttga gggtgcttgt 1950 tccctctccc tgttggtcgg tgggttggta gtttctacag ttgggcagct 2000 ggttaggtag agggagttgt caagtctctg ctggcccagc caaaccctgt 2050 ctgacaacct cttggtgaac cttagtacct aaaaggaaat ctcaccccat 2100 cccacaccct ggaggatttc atctcttgta tatgatgatc tggatccacc 2150 aagacttgtt ttatgctcag ggtcaatttc ttttttcttt tttttttttt 2200 tttttctttt tctttgagac tgggtctcgc tttgttgccc aggctggagt 2250 ggagtggcgt gatcttggct tactgcagcc tttgcctccc cggctcgagc 2300 agtcctgcct cagcctccgg agtagctggg accacaggtt catgccacca 2350 tggccagcca acttttgcat gttttgtaga gatggggtct cacagtgttg 2400 cccaggctgg tctcaaactc ctgggctcag gcgatccacc tgtctcagcc 2450 tcccagagtg ctgggattac aattgtgagc caccacgtcc agctggaagg 2500 gtcaacatct tttacattct gcaagcacat ctgcattttc accccaccct 2550 tcccctcctt ctcccttttt atatcccatt tttatatcga tctcttattt 2600 tacaataaaa ctttgctgcc a 2621 acccccgccc ggcacccgcg tccgcgccat ggccatctac aagcagtcac 750 agcacatgac ggaggttgtg aggcgctgcc gcgctgctca cccaccatga 800 gatagcgatg gtctggcccc tcctcagcat cttatccgag tggaaggaaa 850 tttgcgtgtg gagtatttgg atgacagaaa cacttttcga catagtgtgg 900 tggtgcccta tgagccgcct gaggttggct ctgactgtac caccatccac 950 tacaactaca tgtgtaacag ttcctgcatg ggcggcatga accggaggcc 1000 catcctcacc atcatcacac tggaagactc cagtggtaat ctactgggac 1050 ggaacagctt tgaggtgcgt gtttgtgcct gtcctgggag agaccggcgc 1100 acagaggaag agaatctccg caagaaaggg gagcctcacc acgagctgcc 1150 cccagggagc actaagcgag cactgcccaa caacaccagc tcctctcccc 1200 agccaaagaa gaaaccactg gatggagaat atttcaccct tcagatccgt 1250 gggcgtgagc gcttcgagat gttccgagag ctgaatgagg ccttggaact 1300 caggctggga caaggatgcc aggagccagg ggggagcagg gctcactcca 1350 gtccaaaaag gccacctgaa ggtcagtcta cctcccgcca taaaaaactc 1400 atgttcaaga cagaagggcc tgactcagac tgacattctc cacttcttgt 1450 cagcctccca tccccactga cccccatctc tccctcccct gccattttgg 1500 gttttgggtc tttgaaccct tgcttgc aat aggtgtgcgt cagaagcacc 1550 caggacttcc atttgctttg tcccggggct ccactgaaca agttggcctg 1600 cactggtgtt ttgttgtggg gaggaggatg gggagtagga cataccagct 1650 tagattttaa ggtttttact gtgagggatg tttgggagat gtaagaaatg 1700 ttcttgcagt taagggttag tttacaatca gccacattct aggtaggggc 1750 ccacttcacc gtactaacca gggaagctgt ccctcactgt tgaattttct 1800 ctaacttcaa ggcccatatc tgtgaaatgc tggcatttgc acctacctca 1850 cagagtgcat tgtgagggtt aatgaaataa tgtacatctg gccttgaaac 1900 caccttttat tacatggggt ctagaacttg acccccttga gggtgcttgt 1950 tccctctccc tgttggtcgg tgggttggta gtttctacag ttgggcagct 2000 ggttaggtag agggagttgt caagtctctg ctggcccagc caaaccctgt 2050 ctgacaacct cttggtgaac cttagtacct aaaaggaaat ctcaccccat 2100 cccacaccct ggaggatttc atctcttgta tatgatgatc tggatccacc aagacttgtt 2150 ttatgctcag ggtcaatttc ttttttcttt tttttttttt 2200 tttttctttt tctttgagac tgggtctcgc tttgttgccc aggctggagt 2250 ggagtggcgt gatcttggct tactgcagcc tttgcctccc cggctcgagc 2300 agtcctgcct cagcctccgg agtagctggg accacaggtt catgccacc 2350 tggccagcca acttttgcat gttttgtaga gatggggtct cacagtgttg 2400 cccaggctgg tctcaaactc ctgggctcag gcgatccacc tgtctcagcc 2450 tcccagagtg ctgggattac aattgtgagc caccacgtcc agctggaagg 2500 gtcaacatct tttacattct gcaagcacat ctgcattttc accccaccct 2550 tcccctcctt ctcccttttt atatcccatt tttatatcga tctcttattt 2600 to 2621 tacaataaaa ctttgctgcc

<210> 18 <210> 18

<211> 4400 <211> 4400

<212> ADN <212> DNA

<213> Homo sapiens <213> Homo sapiens

<400> 18 <400> 18

cctcctccac agtggtgagg tcacagcccc ttggagccct ccctcttccc 50 cctcctccac agtggtgagg tcacagcccc ttggagccct ccctcttccc 50

acccctcccg ctcccgggtc tcctttggcc tggggtaacc cgaggtgcag 100 acccctcccg ctcccgggtc tcctttggcc tggggtaacc cgaggtgcag 100

agctgagaat gaggcgattt cggaggatgg agaaatagcc ccgagtcccg 150 agctgagaat gaggcgattt cggaggatgg agaaatagcc ccgagtcccg 150

tggaaaatga ggccggcgga cttgctgcag ctggtgctgc tgctcgacct 200 tggaaaatga ggccggcgga cttgctgcag ctggtgctgc tgctcgacct 200

gcccagggac ctgggcggaa tggggtgttc gtctccaccc tgcgagtgcc 250 gcccagggac ctgggcggaa tggggtgttc gtctccaccc tgcgagtgcc 250

atcaggagga ggacttcaga gtcacctgca aggatattca acgcatcccc 300 atcaggagga ggacttcaga gtcacctgca aggatattca acgcatcccc 300

agcttaccgc ccagtacgca gactctgaag cttattgaga ctcacctgag 350 agcttaccgc ccagtacgca gactctgaag cttattgaga ctcacctgag 350

aactattcca agtcatgcat tttctaatct gcccaatatt tccagaatct 400 aactattcca agtcatgcat tttctaatct gcccaatatt tccagaatct 400

acgtatctat agatgtgact ctgcagcagc tggaatcaca ctccttctac 450 acgtatctat agatgtgact ctgcagcagc tggaatcaca ctccttctac 450

aatttgagta aagtgactca catagaaatt cggaatacca ggaacttaac 500 aatttgagta aagtgactca catagaaatt cggaatacca ggaacttaac 500

ttacatagac cctgatgccc tcaaagagct ccccctccta aagttccttg 550 ttacatagac cctgatgccc tcaaagagct ccccctccta aagttccttg 550

gcattttcaa cactggactt aaaatgttcc ctgacctgac caaagtttat 600 gcattttcaa cactggactt aaaatgttcc ctgacctgac caaagtttat 600

tccactgata tattctttat acttgaaatt acagacaacc cttacatgac 650 tccactgata tattctttat acttgaaatt acagacaacc cttacatgac 650

gtcaatccct gtgaatgctt ttcagggact atgcaatgaa accttgacac 700 gtcaatccct gtgaatgctt ttcagggact atgcaatgaa accttgacac 700

tgaagctgta caacaatggc tttacttcag tccaaggata tgctttcaat 750 tgaagctgta caacaatggc tttacttcag tccaaggata tgctttcaat 750

gggacaaagc tggatgctgt ttacctaaac aagaataaat acctgacagt 800 gggacaaagc tggatgctgt ttacctaaac aagaataaat acctgacagt 800

tattgacaaa gatgcatttg gaggagtata cagtggacca agcttgctgg 850 tattgacaaa gatgcatttg gaggagtata cagtggacca agcttgctgg 850

acgtgtctca aaccagtgtc actgcccttc catccaaagg cctggagcac 900 acgtgtctca aaccagtgtc actgcccttc catccaaagg cctggagcac 900

ctgaaggaac tgatagcaag aaacacctgg actcttaaga aacttccact 950 ctgaaggaac tgatagcaag aaacacctgg actcttaaga aacttccact 950

ttccttgagt ttccttcacc tcacacgggc tgacctttct tacccaagcc 1000 ttccttgagt ttccttcacc tcacacgggc tgacctttct tacccaagcc 1000

actgctgtgc ttttaagaat cagaagaaaa tcagaggaat ccttgagtcc 1050 actgctgtgc ttttaagaat cagaagaaaa tcagaggaat ccttgagtcc 1050

ttgatgtgta atgagagcag tatgcagagc ttgcgccaga gaaaatctgt 1100 ttgatgtgta atgagagcag tatgcagagc ttgcgccaga gaaaatctgt 1100

gaatgccttg aatagccccc tccaccagga atatgaagag aatctgggtg 1150 gaatgccttg aatagccccc tccaccagga atatgaagag aatctgggtg 1150

acagcattgt tgggtacaag gaaaagtcca agttccagga tactcataac 1200 acagcattgt tgggtacaag gaaaagtcca agttccagga tactcataac 1200

aacgctcatt attacgtctt ctttgaagaa caagaggatg agatcattgg 1250 aacgctcatt attacgtctt ctttgaagaa caagaggatg agatcattgg 1250

ttttggccag gagctcaaaa acccccagga agagactcta caagcttttg 1300 ttttggccag gagctcaaaa acccccagga agagactcta caagcttttg 1300

acagccatta tgactacacc atatgtgggg acagtgaaga catggtgtgt 1350 acccccaagt ccgatgagtt caacccgtgt gaagacataa tgggctacaa 1400 gttcctgaga attgtggtgt ggttcgttag tctgctggct ctcctgggca 1450 atgtctttgt cctgcttatt ctcctcacca gccactacaa actgaacgtc 1500 ccccgctttc tcatgtgcaa cctggccttt gcggatttct gcatggggat 1550 gtacctgctc ctcatcgcct ctgtagacct ctacactcac tctgagtact 1600 acaaccatgc catcgactgg cagacaggcc ctgggtgcaa cacggctggt 1650 ttcttcactg tctttgcaag cgagttatcg gtgtatacgc tgacggtcat 1700 caccctggag cgctggtatg ccatcacctt cgccatgcgc ctggaccgga 1750 agatccgcct caggcacgca tgtgccatca tggttggggg ctgggtttgc 1800 tgcttccttc tcgccctgct tcctttggtg ggaataagta gctatgccaa 1850 agtcagtatc tgcctgccca tggacaccga gacccctctt gctctggcat 1900 atattgtttt tgttctgacg ctcaacatag ttgccttcgt catcgtctgc 1950 tgctgttatg tgaagatcta catcacagtc cgaaatccgc agtacaaccc 2000 aggggacaaa gataccaaaa ttgccaagag gatggctgtg ttgatcttca 2050 ccgacttcat atgcatggcc ccaatctcat tctatgctct gtcagcaatt 2100 ctgaacaagc ctctcatcac tgttagcaac tccaaaatct tgctggtact 2150 cttctatcca cttaactcct gtgccaatcc attcctctat gctattttca 2200 ccaaggcctt ccagagggat gtgttcatcc tactcagcaa gtttggcatc 2250 tgtaaacgcc aggctcaggc ataccggggg cagagggttc ctccaaagaa 2300 cagcactgat attcaggttc aaaaggttac ccacgagatg aggcagggtc 2350 tccacaacat ggaagatgtc tatgaactga ttgaaaactc ccatctaacc 2400 ccaaagaagc aaggccaaat ctcagaagag tatatgcaaa cggttttgta 2450 agttaacact acactactca caatggtagg ggaacttaca aaataatagt 2500 ttcttgaata tgcattccaa tcccatgaca cccccaacac atagctgccc 2550 tcactcttgt gcaggcgatg tttcaatgtt tcatggggca agagtttatc 2600 tctggagagt gattagtatt aacctaatca ttgcccccaa gaaggaagtt 2650 aggctaccag catatttgaa tgccaggtga aatcaaaata atctacacta 2700 tctagaagac tttcttgatg ccaagtccag agatgtcatt gtgtaggatg 2750 ttcagtaaat attaactgag ctatgtcaat atagagcttc tcagttttgt 2800 ataacatttc atactaaaga ttcagcaaat ggaaaatgct attaatttgg 2850 ttggtgacca caagataaaa tcagtcccac gttggctcag ttcaactaga 2900 tgttccctga tacaaagaga acttgatttc cttaaaactg aaaagccaaa 2950 cacagctagc tgtcatacaa gaaacagcta ttatgagaca tgaaggaggg 3000 taagaattag ctttaagttt tgttttgctt tgttttgttt tttaactcaa 3050 cctattaatc atctcttcac aagaatccac ctgatgtgac caagctatta 3100 tgtgttgcct ggaaaaactg gcaagatttc agcttatgtg gcctagcaaa 3150 ctaagaattg ctcttcttgg ccagcctcat agcataaaag atgtgaactc 3200 taggaagtct ttctgagtag caataagtgg gaattatggg cagagcacac 3250 tcaatcccct gttgattaat aaaacaggct ggacactaat taactatggg 3300 acttaaatct gtagaaatga aggagtccaa tagcttcttc caattttaaa 3350 actctagtac atccctttcc ctcaaatata tatttctaag ataaagagaa 3400 agaagagcac taagtaagta gaatctgttt ttcctatttt gtagggctgc 3450 tgactcctag tccttgaagc ctagacacat gacccaggaa atttttcctt 3500 tgtttcactt ttgattatga tgtctgagcc aaaaattcaa ttaagtaaac 3550 atactcgcct ggatctgaat cattcattta attactagat ctacccagct 3600 gttatatcag gccaaaaaca gattcgtgtt tatataaaag agtaaacgat 3650 ggttgcaaat tttggctatt tagagttgct acttcactat gaagagtcac 3700 ttcaaaacac ttcgcttgtc tttagggatg atttttgcca tttccagtcc 3750 acggtatgat actaaagctg tcaagagagg tttcttcttt tctgaaactg 3800 ccagctcttt ccagccctgt tgatcactgg acataaagct tcttttcccc 3850 aataattctt ctttacttaa aatagtcagg atctttatct acagatgtac 3900 tctccaggtt acctgtgatg atagccccct aatgtcctgc tagaaaagtc 3950 tccaagcaga gatgacatta cttctgaatg ctcataaacc acaccatgaa 4000 ataaaagctc tttgttgttt taagattgtg aagtgtcgtt aatgggtccc 4050 cacagatggt ccctgctgga ctcacctgga atctctccac agccataccc 4100 actcatcact atcattgaga cctgcacatc ttaatagaaa tattataaac 4150 atcgaaaatc atgacttacc tagaagttcg cttgtaacta atgaaattaa 4200 acaaatgtgt tgccttttgt catgtgtttc tctcctgtga catttcaaaa 4250 tatcacatct tgataaataa tgtgtttcat cttgaatagc tgaactaatt 4300 gctttggaaa cagagtccta gaaaagtgac ttcaacagaa ttgttactaa 4350 aatttgcact cacaacatga aataaatttt cttcctatgg aataatcgtg 4400 acagccatta tgactacacc atatgtgggg acagtgaaga catggtgtgt 1350 acccccaagt ccgatgagtt caacccgtgt gaagacataa tgggctacaa 1400 gttcctgaga attgtggtgt ggttcgttag tctgctggct ctcctgggca 1450 atgtctttgt cctgcttatt gccactacaa ctcctcacca actgaacgtc 1500 ccccgctttc tcatgtgcaa cctggccttt gcggatttct gcatggggat 1550 gtacctgctc ctcatcgcct ctgtagacct ctacactcac tctgagtact 1600 acaaccatgc catcgactgg cagacaggcc ctgggtgcaa cacggctggt 1650 ttcttcactg tctttgcaag cgagttatcg gtgtatacgc tgacggtcat 1700 caccctggag cgctggtatg ccatcacctt cgccatgcgc ctggaccgga 1750 caggcacgca agatccgcct tgtgccatca tggttggggg ctgggtttgc 1800 tgcttccttc tcgccctgct tcctttggtg ggaataagta gctatgccaa 1850 tgcctgccca agtcagtatc tggacaccga gacccctctt gctctggcat 1900 atattgtttt tgttctgacg ctcaacatag ttgccttcgt catcgtctgc 1950 tgctgttatg tgaagatcta catcacagtc cgaaatccgc agtacaaccc 2000 gataccaaaa aggggacaaa ttgccaagag gatggctgtg ttgatcttca 2050 ccgacttcat atgcatggcc ccaatctcat tctatgctct gtcagcaatt ctgaacaagc ctctcatcac tg 2100 ttagcaac tccaaaatct tgctggtact 2150 cttctatcca cttaactcct gtgccaatcc attcctctat gctattttca 2200 ccaaggcctt ccagagggat gtgttcatcc tactcagcaa gtttggcatc 2250 tgtaaacgcc aggctcaggc ataccggggg cagagggttc ctccaaagaa 2300 cagcactgat attcaggttc aaaaggttac ccacgagatg aggcagggtc 2350 tccacaacat ggaagatgtc tatgaactga ttgaaaactc ccatctaacc 2400 ccaaagaagc aaggccaaat ctcagaagag tatatgcaaa cggttttgta 2450 acactactca agttaacact ggaacttaca caatggtagg aaataatagt 2500 tgcattccaa ttcttgaata tcccatgaca cccccaacac atagctgccc 2550 tcactcttgt gcaggcgatg tttcaatgtt tcatggggca agagtttatc 2600 tctggagagt gattagtatt aacctaatca ttgcccccaa gaaggaagtt 2650 catatttgaa aggctaccag aatcaaaata tgccaggtga atctacacta 2700 tctagaagac tttcttgatg ccaagtccag agatgtcatt gtgtaggatg 2750 ttcagtaaat attaactgag ctatgtcaat atagagcttc tcagttttgt 2800 ataacatttc atactaaaga ttcagcaaat ggaaaatgct attaatttgg 2850 caagataaaa ttggtgacca tcagtcccac gttggctcag ttcaactaga 2900 tacaaagaga tgttccctga acttgatttc cttaaaactg aaaa gccaaa 2950 tgtcatacaa cacagctagc gaaacagcta ttatgagaca tgaaggaggg 3000 taagaattag ctttaagttt tgttttgctt tgttttgttt tttaactcaa 3050 cctattaatc atctcttcac aagaatccac ctgatgtgac caagctatta 3100 tgtgttgcct ggaaaaactg gcaagatttc agcttatgtg gcctagcaaa 3150 ctaagaattg ctcttcttgg ccagcctcat agcataaaag atgtgaactc 3200 taggaagtct ttctgagtag caataagtgg gaattatggg cagagcacac 3250 tcaatcccct gttgattaat aaaacaggct ggacactaat taactatggg 3300 acttaaatct gtagaaatga tagcttcttc aggagtccaa caattttaaa 3350 actctagtac atccctttcc ctcaaatata tatttctaag ataaagagaa 3400 agaagagcac taagtaagta gaatctgttt ttcctatttt gtagggctgc 3450 tgactcctag tccttgaagc ctagacacat gacccaggaa atttttcctt 3500 tgtttcactt ttgattatga tgtctgagcc aaaaattcaa ttaagtaaac 3550 atactcgcct ggatctgaat cattcattta attactagat ctacccagct 3600 gttatatcag gccaaaaaca gattcgtgtt tatataaaag agtaaacgat 3650 ggttgcaaat tttggctatt tagagttgct acttcactat gaagagtcac 3700 ttcaaaacac ttcgcttgtc tttagggatg atttttgcca tttccagtcc 3750 acggtatgat to ctaaagctg tcaagagagg tttcttcttt tctgaaactg 3800 ccagctcttt ccagccctgt tgatcactgg acataaagct tcttttcccc 3850 aataattctt ctttacttaa aatagtcagg atctttatct acagatgtac 3900 tctccaggtt acctgtgatg atagccccct aatgtcctgc tagaaaagtc 3950 gatgacatta tccaagcaga cttctgaatg ctcataaacc acaccatgaa 4000 ataaaagctc tttgttgttt taagattgtg aagtgtcgtt aatgggtccc 4050 ccctgctgga cacagatggt ctcacctgga atctctccac agccataccc 4100 atcattgaga actcatcact cctgcacatc ttaatagaaa tattataaac 4150 atcgaaaatc atgacttacc tagaagttcg cttgtaacta atgaaattaa 4200 acaaatgtgt tgccttttgt catgtgtttc tctcctgtga catttcaaaa 4250 tatcacatct tgataaataa tgtgtttcat cttgaatagc tgaactaatt 4300 gctttggaaa cagagtccta ttcaacagaa gaaaagtgac ttgttactaa 4350 aatttgcact cacaacatga aataaatttt cttcctatgg aataatcgtg 4400

<210> 19 <210> 19

<211> 1715 <211> 1715

<212> ADN <212> DNA

<213> Homo sapiens <213> Homo sapiens

<400> 19 <400> 19

gaattccagc ggcggcgccg ttgccgctgc cgggaaacac aaggaaaggg 50 gaattccagc ggcggcgccg ttgccgctgc cgggaaacac aaggaaaggg 50

aaccagcgca gcgtggcgat gggcgggggt agagccccgc cggagaggct 100 aaccagcgca gcgtggcgat gggcgggggt agagccccgc cggagaggct 100

gggcggctgc cggtgacaga ctgtgccctg tccacggtgc ctcctgcatg 150 gggcggctgc cggtgacaga ctgtgccctg tccacggtgc ctcctgcatg 150

tcctgctgcc ctgagctgtc ccgagctagg tgacagcgta ccacgctgcc 200 accatgaatg aggtgtctgt catcaaagaa ggctggctcc acaagcgtgg 250 tgaatacatc aagacctgga ggccacggta cttcctgctg aagagcgacg 300 gctccttcat tgggtacaag gagaggcccg aggcccctga tcagactcta 350 ccccccttaa acaacttctc cgtagcagaa tgccagctga tgaagaccga 400 gaggccgcga cccaacacct ttgtcatacg ctgcctgcag tggaccacag 450 tcatcgagag gaccttccac gtggattctc cagacgagag ggaggagtgg 500 atgcgggcca tccagatggt cgccaacagc ctcaagcagc gggccccagg 550 cgaggacccc atggactaca agtgtggctc ccccagtgac tcctccacga 600 ctgaggagat ggaagtggcg gtcagcaagg cacgggctaa agtgaccatg 650 aatgacttcg actatctcaa actccttggc aagggaacct ttggcaaagt 700 catcctggtg cgggagaagg ccactggccg ctactacgcc atgaagatcc 750 tgcgaaagga agtcatcatt gccaaggatg aagtcgctca cacagtcacc 800 gagagccggg tcctccagaa caccaggcac ccgttcctca ctgcgctgaa 850 gtatgccttc cagacccacg accgcctgtg ctttgtgatg gagtatgcca 900 acgggggtga gctgttcttc cacctgtccc gggagcgtgt cttcacagag 950 gagcgggccc ggttttatgg tgcagagatt gtctcggctc ttgagtactt 1000 gcactcgcgg gacgtggtat accgcgacat caagctggaa aacctcatgc 1050 tggacaaaga tggccacatc aagatcactg actttggcct ctgcaaagag 1100 ggcatcagtg acggggccac catgaaaacc ttctgtggga ccccggagta 1150 cctggcgcct gaggtgctgg aggacaatga ctatggccgg gccgtggact 1200 ggtgggggct gggtgtggtc atgtacgaga tgatgtgcgg ccgcctgccc 1250 ttctacaacc aggaccacga gcgcctcttc gagctcatcc tcatggaaga 1300 gatccgcttc ccgcgcacgc tcagccccga ggccaagtcc ctgcttgctg 1350 ggctgcttaa gaaggacccc aagcagaggc ttggtggggg gcccagcgat 1400 gccaaggagg tcatggagca caggttcttc ctcagcatca actggcagga 1450 cgtggtccag aagaagctcc tgccaccctt caaacctcag gtcacgtccg 1500 aggtcgacac aaggtacttc gatgatgaat ttaccgccca gtccatcaca 1550 atcacacccc ctgaccgcta tgacagcctg ggcttactgg agctggacca 1600 gcggacccac ttcccccagt tctcctactc ggccagcatc cgcgagtgag 1650 cagtctgccc acgcagagga cgcacgctcg ctgccatcac cgctgggtgg 1700 ttttttaccc ctgcc 1715 tcctgctgcc ctgagctgtc ccgagctagg tgacagcgta ccacgctgcc 200 accatgaatg aggtgtctgt catcaaagaa ggctggctcc acaagcgtgg 250 aagacctgga tgaatacatc ggccacggta cttcctgctg aagagcgacg 300 gctccttcat tgggtacaag gagaggcccg tcagactcta aggcccctga 350 acaacttctc ccccccttaa cgtagcagaa tgccagctga tgaagaccga 400 gaggccgcga cccaacacct ttgtcatacg ctgcctgcag tggaccacag 450 tcatcgagag gaccttccac gtggattctc cagacgagag ggaggagtgg 500 atgcgggcca tccagatggt cgccaacagc ctcaagcagc gggccccagg 550 atggactaca cgaggacccc agtgtggctc ccccagtgac tcctccacga 600 ctgaggagat ggaagtggcg gtcagcaagg cacgggctaa agtgaccatg 650 aatgacttcg actatctcaa actccttggc aagggaacct ttggcaaagt 700 catcctggtg cgggagaagg ccactggccg ctactacgcc atgaagatcc 750 tgcgaaagga agtcatcatt gccaaggatg aagtcgctca cacagtcacc 800 tcctccagaa gagagccggg ccgttcctca caccaggcac ctgcgctgaa 850 gtatgccttc cagacccacg accgcctgtg ctttgtgatg gagtatgcca 900 acgggggtga gctgttcttc cacctgtccc gggagcgtgt cttcacagag 950 gagcgggccc ggttttatgg tgcagagatt gtctcggc tc ttgagtactt 1000 gcactcgcgg gacgtggtat accgcgacat caagctggaa aacctcatgc 1050 tggacaaaga tggccacatc aagatcactg actttggcct ctgcaaagag 1100 ggcatcagtg acggggccac catgaaaacc ttctgtggga ccccggagta 1150 cctggcgcct gaggtgctgg aggacaatga ctatggccgg gccgtggact 1200 ggtgggggct gggtgtggtc atgtacgaga tgatgtgcgg ccgcctgccc 1250 ttctacaacc aggaccacga gcgcctcttc gagctcatcc tcatggaaga 1300 gatccgcttc ccgcgcacgc tcagccccga ggccaagtcc ctgcttgctg 1350 ggctgcttaa gaaggacccc aagcagaggc ttggtggggg gcccagcgat 1400 tcatggagca gccaaggagg ctcagcatca caggttcttc actggcagga 1450 cgtggtccag aagaagctcc tgccaccctt caaacctcag gtcacgtccg 1500 aggtcgacac aaggtacttc gatgatgaat ttaccgccca gtccatcaca 1550 atcacacccc ctgaccgcta tgacagcctg ggcttactgg agctggacca 1600 gcggacccac ttcccccagt tctcctactc ggccagcatc cgcgagtgag 1650 acgcagagga cagtctgccc cgcacgctcg ctgccatcac cgctgggtgg ttttttaccc ctgcc 1700 1715

<210> 20 <210> 20

<211> 1327 <211> 1327

<212> ADN <212> DNA

<213> Homo sapiens <400> 20 <213> Homo sapiens <400> 20

cacaacggcc atcaccacct ctccgcaccc tctgtctcct tccttctcgg 50 cacaacggcc atcaccacct ctccgcaccc tctgtctcct tccttctcgg 50

gcctcacccc tggccctcgc tttcagtgcc cagcccggac cgcagcactc 100 gcctcacccc tggccctcgc tttcagtgcc cagcccggac cgcagcactc 100

cagttccgcc ccaacccggg aaccctggac tgaggctccc gtttctgtcc 150 cagttccgcc ccaacccggg aaccctggac tgaggctccc gtttctgtcc 150

tttctattgg gcgcacttcc gatggcgtca ggaatttcag ccaataggag 200 tttctattgg gcgcacttcc gatggcgtca ggaatttcag ccaataggag 200

ccagccagga agtacctctc tgagcggttg gtgccgggta taaaagaagg 250 ccagccagga agtacctctc tgagcggttg gtgccgggta taaaagaagg 250

ccagcacggc tgctcacgac gccgcgaagc ctgtgtagca ctgagacatc 300 ccagcacggc tgctcacgac gccgcgaagc ctgtgtagca ctgagacatc 300

agtgagttgg ctacagcaga ccaaacagcc cagcagccca gcagcccacg 350 agtgagttgg ctacagcaga ccaaacagcc cagcagccca gcagcccacg 350

catgcggcgc ctcacagtcg atgactttga aatcgggcgt cccctgggca 400 catgcggcgc ctcacagtcg atgactttga aatcgggcgt cccctgggca 400

aggggaaatt tgggaatgtg tacctggctc ggctcaagga aagccatttc 450 aggggaaatt tgggaatgtg tacctggctc ggctcaagga aagccatttc 450

attgtggccc tgaaggttct cttcaagtcg cagatagaga aggaaggact 500 attgtggccc tgaaggttct cttcaagtcg cagatagaga aggaaggact 500

ggagcaccag ctgcgccggg aaattgagat ccaggctcat ctacaacacc 550 ggagcaccag ctgcgccggg aaattgagat ccaggctcat ctacaacacc 550

ccaatatcct gcgcctgtat aactatttcc atgatgcacg ccgggtgtac 600 ccaatatcct gcgcctgtat aactatttcc atgatgcacg ccgggtgtac 600

ctgattctgg aatatgctcc aaggggtgag ctctacaagg agctgcagaa 650 ctgattctgg aatatgctcc aaggggtgag ctctacaagg agctgcagaa 650

aagcgagaaa ttagatgaac agcgcacagc cacgataata gaggaagttg 700 aagcgagaaa ttagatgaac agcgcacagc cacgataata gaggaagttg 700

cagatgccct gacctactgc catgacaaga aagtgattca cagagatatt 750 cagatgccct gacctactgc catgacaaga aagtgattca cagagatatt 750

aagccagaga acctgctgct ggggttcagg ggtgaggtga agattgcaga 800 aagccagaga acctgctgct ggggttcagg ggtgaggtga agattgcaga 800

ttttggctgg tctgtgcaca cccccctccc tgagaggaag acaatgtgtg 850 ttttggctgg tctgtgcaca cccccctccc tgagaggaag acaatgtgtg 850

ggacactgga ctacttgccg ccagaaatga ttgaggggag aacatatgat 900 ggacactgga ctacttgccg ccagaaatga ttgaggggag aacatatgat 900

gaaaaggtgg atttgtggtg cattggagtg ctctgctatg agctgctggt 950 gaaaaggtgg atttgtggtg cattggagtg ctctgctatg agctgctggt 950

gggatatcca ccctttgaga gcgcctccca cagtgagact tacagacgca 1000 gggatatcca ccctttgaga gcgcctccca cagtgagact tacagacgca 1000

tcctcaaggt agatgtgagg tttccactat caatgcctct gggggcccgg 1050 tcctcaaggt agatgtgagg tttccactat caatgcctct gggggcccgg 1050

gacttgattt ccaggcttct cagataccag cccttggaga gactgcccct 1100 gacttgattt ccaggcttct cagataccag cccttggaga gactgcccct 1100

ggcccagatc ctgaagcacc cctgggttca ggcccactcc cgaagggtgc 1150 ggcccagatc ctgaagcacc cctgggttca ggcccactcc cgaagggtgc 1150

tgcctccctg tgctcagatg gcttcctgag ccctgtctgc ctctgttccc 1200 tgcctccctg tgctcagatg gcttcctgag ccctgtctgc ctctgttccc 1200

tttgtgtgtg ttcagggagc tctcctgctc tgccacctca tttgtcttta 1250 tttgtgtgtg ttcagggagc tctcctgctc tgccacctca tttgtcttta 1250

tttttttctc ttttaagatg taagatgcta attaataaaa gctgaatcat 1300 tttttttctc ttttaagatg taagatgcta attaataaaa gctgaatcat 1300

ttcataccaa aaaaaaaaaa aaaaaaa 1327 ttcataccaa aaaaaaaaaa aaaaaaa 1327

<210> 21 <210> 21

<211> 2575 <211> 2575

<212> ADN <212> DNA

<213> Homo sapiens <213> Homo sapiens

<400> 21<400> 21

ggaggaggaa gcaagcgagg gggctggttc ctgagcttcg caattcctgt 50 gtcgccttct gggctcccag cctgccgggt cgcatgatcc ctccggccgg 100 agctggtttt tttgccagcc accgcgaggc cggctgagtt accggcatcc 150 ccgcagccac ctcctctccc gacctgtgat acaaaagatc ttccgggggc 200 tgcacctgcc tgcctttgcc taaggcggat ttgaatctct ttctctccct 250 tcagaatctt atcttggctt tggatcttag aagagaatca ctaaccagag 300 acgagactca gtgagtgagc aggtgttttg gacaatggac tggttgagcc 350 catccctatt ataaaaatgt ctcagagcaa ccgggagctg gtggttgact 400 ttctctccta caagctttcc cagaaaggat acagctggag tcagtttagt 450 gatgtggaag agaacaggac tgaggcccca gaagggactg aatcggagat 500 ggagaccccc agtgccatca atggcaaccc atcctggcac ctggcagaca 550 gccccgcggt gaatggagcc actggccaca gcagcagttt ggatgcccgg 600 gaggtgatcc ccatggcagc agtaaagcaa gcgctgaggg aggcaggcga 650 cgagtttgaa ctgcggtacc ggcgggcatt cagtgacctg acatcccagc 700 tccacatcac cccagggaca gcatatcaga gctttgaaca ggtagtgaat 750 gaactcttcc gggatggggt aaactggggt cgcattgtgg cctttttctc 800 cttcggcggg gcactgtgcg tggaaagcgt agacaaggag atgcaggtat 850 tggtgagtcg gatcgcagct tggatggcca cttacctgaa tgaccaccta 900 gagccttgga tccaggagaa cggcggctgg gatacttttg tggaactcta 950 tgggaacaat gcagcagccg agagccgaaa gggccaggaa cgcttcaacc 1000 gctggttcct gacgggcatg actgtggccg gcgtggttct gctgggctca 1050 ctcttcagtc ggaaatgacc agacactgac catccactct accctcccac 1100 ccccttctct gctccaccac atcctccgtc cagccgccat tgccaccagg 1150 agaaccacta catgcagccc atgcccacct gcccatcaca gggttgggcc 1200 cagatctggt cccttgcagc tagttttcta gaatttatca cacttctgtg 1250 agacccccac acctcagttc ccttggcctc agaattcaca aaatttccac 1300 aaaatctgtc caaaggaggc tggcaggtat ggaagggttt gtggctgggg 1350 gcaggagggc cctacctgat tggtgcaacc cttacccctt agcctccctg 1400 aaaatgtttt tctgccaggg agcttgaaag ttttcagaac ctcttcccca 1450 gaaaggagac tagattgcct ttgttttgat gtttgtggcc tcagaattga 1500 tcattttccc cccactctcc ccacactaac ctgggttccc tttccttcca 1550 tccctacccc ctaagagcca tttaggggcc acttttgact agggattcag 1600 gctgcttggg ataaagatgc aaggaccagg actccctcct cacctctgga 1650 ctggctagag tcctcactcc cagtccaaat gtcctccaga agcctctggc 1700 tagaggccag ccccacccag gagggagggg gctatagcta caggaagcac 1750 cccatgccaa agctagggtg gcccttgcag ttcagcacca ccctagtccc 1800 ttcccctccc tggctcccat gaccatactg agggaccaac tgggcccaag 1850 acagatgccc cagagctgtt tatggcctca gctgcctcac ttcctacaag 1900 agcagcctgt ggcatctttg ccttgggctg ctcctcatgg tgggttcagg 1950 ggactcagcc ctgaggtgaa agggagctat caggaacagc tatgggagcc 2000 ccagggtctt ccctacctca ggcaggaagg gcaggaagga gagcctgctg 2050 catggggtgg ggtagggctg actagaaggg ccagtcctgc ctggccaggc 2100 agatctgtgc cccatgcctg tccagcctgg gcagccaggc tgccaaggcc 2150 agagtggcct ggccaggagc tcttcaggcc tccctctctc ttctgctcca 2200 cccttggcct gtctcatccc caggggtccc agccaccccg ggctctctgc 2250 tgtacatatt tgagactagt ttttattcct tgtgaagatg atatactatt 2300 tttgttaagc gtgtctgtat ttatgtgtga ggagctgctg gcttgcagtg 2350 cgcgtgcacg tggagagctg gtgcccggag attggacggc ctgatgctcc 2400 ctcccctgcc ctggtccagg gaagctggcc gagggtcctg gctcctgagg 2450 ggcatctgcc cctcccccaa cccccacccc acacttgttc cagctctttg 2500 aaatagtctg tgtgaaggtg aaagtgcagt tcagtaataa actgtgttta 2550 ctcagtgaaa aaaaaaaaaa aaaaa 2575 ggaggaggaa gcaagcgagg gggctggttc ctgagcttcg caattcctgt 50 gtcgccttct gggctcccag cctgccgggt cgcatgatcc ctccggccgg 100 agctggtttt tttgccagcc accgcgaggc cggctgagtt accggcatcc 150 ccgcagccac ctcctctccc gacctgtgat acaaaagatc ttccgggggc 200 tgcacctgcc tgcctttgcc taaggcggat ttgaatctct ttctctccct 250 tcagaatctt atcttggctt tggatcttag aagagaatca ctaaccagag 300 acgagactca gtgagtgagc aggtgttttg gacaatggac tggttgagcc 350 catccctatt ataaaaatgt ctcagagcaa ccgggagctg gtggttgact 400 ttctctccta caagctttcc cagaaaggat acagctggag tcagtttagt 450 gatgtggaag agaacaggac tgaggcccca gaagggactg aatcggagat 500 agtgccatca ggagaccccc atcctggcac atggcaaccc ctggcagaca 550 gccccgcggt gaatggagcc actggccaca gcagcagttt ggatgcccgg 600 gaggtgatcc ccatggcagc agtaaagcaa gcgctgaggg aggcaggcga 650 cgagtttgaa ctgcggtacc ggcgggcatt cagtgacctg acatcccagc 700 cccagggaca tccacatcac gcatatcaga gctttgaaca ggtagtgaat 750 gaactcttcc gggatggggt aaactggggt cgcattgtgg cctttttctc 800 cttcggcggg gcactgtgcg tggaaagcgt agacaagg ag atgcaggtat 850 tggtgagtcg gatcgcagct tggatggcca tgaccaccta cttacctgaa 900 tccaggagaa gagccttgga cggcggctgg gatacttttg tggaactcta 950 tgggaacaat gcagcagccg agagccgaaa gggccaggaa cgcttcaacc 1000 gctggttcct gacgggcatg actgtggccg gcgtggttct gctgggctca 1050 ctcttcagtc ggaaatgacc agacactgac catccactct accctcccac 1100 ccccttctct gctccaccac atcctccgtc cagccgccat tgccaccagg 1150 agaaccacta catgcagccc atgcccacct gcccatcaca gggttgggcc 1200 cccttgcagc cagatctggt tagttttcta gaatttatca cacttctgtg 1250 agacccccac acctcagttc ccttggcctc agaattcaca aaatttccac 1300 aaaatctgtc caaaggaggc tggcaggtat ggaagggttt gtggctgggg 1350 gcaggagggc cctacctgat tggtgcaacc cttacccctt agcctccctg 1400 aaaatgtttt tctgccaggg agcttgaaag ttttcagaac ctcttcccca 1450 gaaaggagac tagattgcct ttgttttgat gtttgtggcc tcagaattga 1500 tcattttccc cccactctcc ccacactaac ctgggttccc tttccttcca 1550 tccctacccc ctaagagcca tttaggggcc acttttgact agggattcag 1600 gctgcttggg ataaagatgc aaggaccagg actccctcct cacctctgga 1650 ctggcta gag tcctcactcc cagtccaaat gtcctccaga agcctctggc 1700 tagaggccag ccccacccag gagggagggg gctatagcta caggaagcac 1750 cccatgccaa agctagggtg gcccttgcag ttcagcacca ccctagtccc 1800 ttcccctccc tggctcccat gaccatactg agggaccaac tgggcccaag 1850 acagatgccc cagagctgtt tatggcctca gctgcctcac ttcctacaag 1900 agcagcctgt ggcatctttg ccttgggctg ctcctcatgg tgggttcagg 1950 ggactcagcc ctgaggtgaa agggagctat caggaacagc tatgggagcc 2000 ccctacctca ccagggtctt ggcaggaagg gcaggaagga gagcctgctg 2050 catggggtgg ggtagggctg actagaaggg ccagtcctgc ctggccaggc 2100 agatctgtgc cccatgcctg tccagcctgg gcagccaggc tgccaaggcc 2150 agagtggcct ggccaggagc tcttcaggcc tccctctctc ttctgctcca 2200 cccttggcct gtctcatccc caggggtccc agccaccccg ggctctctgc 2250 tgtacatatt tgagactagt ttttattcct tgtgaagatg atatactatt 2300 tttgttaagc gtgtctgtat ttatgtgtga ggagctgctg gcttgcagtg 2350 cgcgtgcacg tggagagctg gtgcccggag attggacggc ctgatgctcc 2400 ctcccctgcc ctggtccagg gaagctggcc gagggtcctg gctcctgagg 2450 ggcatctgcc cctcccccaa cccccaccc c acacttgttc cagctctttg 2500 aaatagtctg tgtgaaggtg aaagtgcagt tcagtaataa actgtgttta 2550 ctcagtgaaa aaaaaaaaaa aaaaa 2575

<210> 22 <210> 22

<211> 1154 <211> 1154

<212> ADN <212> DNA

<213> Homo sapiens <213> Homo sapiens

<400> 22 <400> 22

cgctcaggga aggcgggtgc gcgcctgcgg ggcggagatg ggcagggggc 50 cgctcaggga aggcgggtgc gcgcctgcgg ggcggagatg ggcagggggc 50

ggtgcgtggg tcccagtctg cagttaaggg ggcaggagtg gcgctgctca 100 ggtgcgtggg tcccagtctg cagttaaggg ggcaggagtg gcgctgctca 100

cctctggtgc caaagggcgg cgcagcggct gccgagctcg gccctggagg 150 cctctggtgc caaagggcgg cgcagcggct gccgagctcg gccctggagg 150

cggcgagaac atggtgcgca ggttcttggt gaccctccgg attcggcgcg 200 cggcgagaac atggtgcgca ggttcttggt gaccctccgg attcggcgcg 200

cgtgcggccc gccgcgagtg agggttttcg tggttcacat cccgcggctc 250 cgtgcggccc gccgcgagtg agggttttcg tggttcacat cccgcggctc 250

acgggggagt gggcagcgcc aggggcgccc gccgctgtgg ccctcgtgct 300 acgggggagt gggcagcgcc aggggcgccc gccgctgtgg ccctcgtgct 300

gatgctactg aggagccagc gtctagggca gcagccgctt cctagaagac 350 gatgctactg aggagccagc gtctagggca gcagccgctt cctagaagac 350

caggtcatga tgatgggcag cgcccgagtg gcggagctgc tgctgctcca 400 caggtcatga tgatgggcag cgcccgagtg gcggagctgc tgctgctcca 400

cggcgcggag cccaactgcg ccgaccccgc cactctcacc cgacccgtgc 450 cggcgcggag cccaactgcg ccgaccccgc cactctcacc cgacccgtgc 450

acgacgctgc ccgggagggc ttcctggaca cgctggtggt gctgcaccgg 500 acgacgctgc ccgggagggc ttcctggaca cgctggtggt gctgcaccgg 500

gccggggcgc ggctggacgt gcgcgatgcc tggggccgtc tgcccgtgga 550 gccggggcgc ggctggacgt gcgcgatgcc tggggccgtc tgcccgtgga 550

cctggctgag gagctgggcc atcgcgatgt cgcacggtac ctgcgcgcgg 600 cctggctgag gagctgggcc atcgcgatgt cgcacggtac ctgcgcgcgg 600

ctgcgggggg caccagaggc agtaaccatg cccgcataga tgccgcggaa 650 ctgcgggggg caccagaggc agtaaccatg cccgcataga tgccgcggaa 650

ggtccctcag acatccccga ttgaaagaac cagagaggct ctgagaaacc 700 ggtccctcag acatccccga ttgaaagaac cagagaggct ctgagaaacc 700

tcgggaaact tagatcatca gtcaccgaag gtcctacagg gccacaactg 750 tcgggaaact tagatcatca gtcaccgaag gtcctacagg gccacaactg 750

cccccgccac aacccacccc gctttcgtag ttttcattta gaaaatagag 800 cccccgccac aacccacccc gctttcgtag ttttcattta gaaaatagag 800

cttttaaaaa tgtcctgcct tttaacgtag atatatgcct tcccccacta 850 ccgtaaatgt ccatttatat cattttttat atattcttat aaaaatgtaa 900 aaaagaaaaa caccgcttct gccttttcac tgtgttggag ttttctggag 950 tgagcactca cgccctaagc gcacattcat gtgggcattt cttgcgagcc 1000 tcgcagcctc cggaagctgt cgacttcatg acaagcattt tgtgaactag 1050 ggaagctcag gggggttact ggcttctctt gagtcacact gctagcaaat 1100 ggcagaacca aagctcaaat aaaaataaaa taattttcat tcattcactc 1150 aaaa 1154 cttttaaaaa tgtcctgcct tttaacgtag atatatgcct tcccccacta 850 ccgtaaatgt ccatttatat cattttttat atattcttat aaaaatgtaa 900 aaaagaaaaa caccgcttct gccttttcac tgtgttggag ttttctggag 950 tgagcactca cgccctaagc gcacattcat gtgggcattt cttgcgagcc 1000 tcgcagcctc cggaagctgt cgacttcatg acaagcattt tgtgaactag 1050 ggaagctcag gggggttact ggcttctctt gagtcacact gctagcaaat 1100 ggcagaacca aagctcaaat aaaaataaaa taattttcat tcattcactc 1150 aaaa 1154

<210> 23 <210> 23

<211> 5511 <211> 5511

<212> ADN <212> DNA

<213> Homo sapiens <213> Homo sapiens

<400> 23 <400> 23

acacacacac acccctcccc tgccatccct ccccggactc cggctccggc 50 acacacacac acccctcccc tgccatccct ccccggactc cggctccggc 50

tccgattgca atttgcaacc tccgctgccg tcgccgcagc agccaccaat 100 tccgattgca atttgcaacc tccgctgccg tcgccgcagc agccaccaat 100

tcgccagcgg ttcaggtggc tcttgcctcg atgtcctagc ctaggggccc 150 tcgccagcgg ttcaggtggc tcttgcctcg atgtcctagc ctaggggccc 150

ccgggccgga cttggctggg ctcccttcac cctctgcgga gtcatgaggg 200 ccgggccgga cttggctggg ctcccttcac cctctgcgga gtcatgaggg 200

cgaacgacgc tctgcaggtg ctgggcttgc ttttcagcct ggcccggggc 250 cgaacgacgc tctgcaggtg ctgggcttgc ttttcagcct ggcccggggc 250

tccgaggtgg gcaactctca ggcagtgtgt cctgggactc tgaatggcct 300 tccgaggtgg gcaactctca ggcagtgtgt cctgggactc tgaatggcct 300

gagtgtgacc ggcgatgctg agaaccaata ccagacactg tacaagctct 350 gagtgtgacc ggcgatgctg agaaccaata ccagacactg tacaagctct 350

acgagaggtg tgaggtggtg atggggaacc ttgagattgt gctcacggga 400 acgagaggtg tgaggtggtg atggggaacc ttgagattgt gctcacggga 400

cacaatgccg acctctcctt cctgcagtgg attcgagaag tgacaggcta 450 cacaatgccg acctctcctt cctgcagtgg attcgagaag tgacaggcta 450

tgtcctcgtg gccatgaatg aattctctac tctaccattg cccaacctcc 500 tgtcctcgtg gccatgaatg aattctctac tctaccattg cccaacctcc 500

gcgtggtgcg agggacccag gtctacgatg ggaagtttgc catcttcgtc 550 gcgtggtgcg agggacccag gtctacgatg ggaagtttgc catcttcgtc 550

atgttgaact ataacaccaa ctccagccac gctctgcgcc agctccgctt 600 atgttgaact ataacaccaa ctccagccac gctctgcgcc agctccgctt 600

gactcagctc accgagattc tgtcaggggg tgtttatatt gagaagaacg 650 gactcagctc accgagattc tgtcaggggg tgtttatatt gagaagaacg 650

ataagctttg tcacatggac acaattgact ggagggacat cgtgagggac 700 ataagctttg tcacatggac acaattgact ggagggacat cgtgagggac 700

cgagatgctg agatagtggt gaaggacaat ggcagaagct gtcccccctg 750 cgagatgctg agatagtggt gaaggacaat ggcagaagct gtcccccctg 750

tcatgaggtt tgcaaggggc gatgctgggg tcctggatca gaagactgcc 800 tcatgaggtt tgcaaggggc gatgctgggg tcctggatca gaagactgcc 800

agacattgac caagaccatc tgtgctcctc agtgtaatgg tcactgcttt 850 agacattgac caagaccatc tgtgctcctc agtgtaatgg tcactgcttt 850

gggcccaacc ccaaccagtg ctgccatgat gagtgtgccg ggggctgctc 900 gggcccaacc ccaaccagtg ctgccatgat gagtgtgccg ggggctgctc 900

aggccctcag gacacagact gctttgcctg ccggcacttc aatgacagtg 950 aggccctcag gacacagact gctttgcctg ccggcacttc aatgacagtg 950

gagcctgtgt acctcgctgt ccacagcctc ttgtctacaa caagctaact 1000 gagcctgtgt acctcgctgt ccacagcctc ttgtctacaa caagctaact 1000

ttccagctgg aacccaatcc ccacaccaag tatcagtatg gaggagtttg 1050 ttccagctgg aacccaatcc ccacaccaag tatcagtatg gaggagtttg 1050

tgtagccagc tgtccccata actttgtggt ggatcaaaca tcctgtgtca 1100 tgtagccagc tgtccccata actttgtggt ggatcaaaca tcctgtgtca 1100

gggcctgtcc tcctgacaag atggaagtag ataaaaatgg gctcaagatg 1150 gggcctgtcc tcctgacaag atggaagtag ataaaaatgg gctcaagatg 1150

tgtgagcctt gtgggggact atgtcccaaa gcctgtgagg gaacaggctc 1200 tgggagccgc ttccagactg tggactcgag caacattgat ggatttgtga 1250 actgcaccaa gatcctgggc aacctggact ttctgatcac cggcctcaat 1300 ggagacccct ggcacaagat ccctgccctg gacccagaga agctcaatgt 1350 cttccggaca gtacgggaga tcacaggtta cctgaacatc cagtcctggc 1400 cgccccacat gcacaacttc agtgtttttt ccaatttgac aaccattgga 1450 ggcagaagcc tctacaaccg gggcttctca ttgttgatca tgaagaactt 1500 gaatgtcaca tctctgggct tccgatccct gaaggaaatt agtgctgggc 1550 gtatctatat aagtgccaat aggcagctct gctaccacca ctctttgaac 1600 tggaccaagg tgcttcgggg gcctacggaa gagcgactag acatcaagca 1650 taatcggccg cgcagagact gcgtggcaga gggcaaagtg tgtgacccac 1700 tgtgctcctc tgggggatgc tggggcccag gccctggtca gtgcttgtcc 1750 tgtcgaaatt atagccgagg aggtgtctgt gtgacccact gcaactttct 1800 gaatggggag cctcgagaat ttgcccatga ggccgaatgc ttctcctgcc 1850 acccggaatg ccaacccatg gagggcactg ccacatgcaa tggctcgggc 1900 tctgatactt gtgctcaatg tgcccatttt cgagatgggc cccactgtgt 1950 gagcagctgc ccccatggag tcctaggtgc caagggccca atctacaagt 2000 acccagatgt tcagaatgaa tgtcggccct gccatgagaa ctgcacccag 2050 gggtgtaaag gaccagagct tcaagactgt ttaggacaaa cactggtgct 2100 gatcggcaaa acccatctga caatggcttt gacagtgata gcaggattgg 2150 tagtgatttt catgatgctg ggcggcactt ttctctactg gcgtgggcgc 2200 cggattcaga ataaaagggc tatgaggcga tacttggaac ggggtgagag 2250 catagagcct ctggacccca gtgagaaggc taacaaagtc ttggccagaa 2300 tcttcaaaga gacagagcta aggaagctta aagtgcttgg ctcgggtgtc 2350 tttggaactg tgcacaaagg agtgtggatc cctgagggtg aatcaatcaa 2400 gattccagtc tgcattaaag tcattgagga caagagtgga cggcagagtt 2450 ttcaagctgt gacagatcat atgctggcca ttggcagcct ggaccatgcc 2500 cacattgtaa ggctgctggg actatgccca gggtcatctc tgcagcttgt 2550 cactcaatat ttgcctctgg gttctctgct ggatcatgtg agacaacacc 2600 ggggggcact ggggccacag ctgctgctca actggggagt acaaattgcc 2650 aagggaatgt actaccttga ggaacatggt atggtgcata gaaacctggc 2700 tgcccgaaac gtgctactca agtcacccag tcaggttcag gtggcagatt 2750 ttggtgtggc tgacctgctg cctcctgatg ataagcagct gctatacagt 2800 gaggccaaga ctccaattaa gtggatggcc cttgagagta tccactttgg 2850 gaaatacaca caccagagtg atgtctggag ctatggtgtg acagtttggg 2900 agttgatgac cttcggggca gagccctatg cagggctacg attggctgaa 2950 gtaccagacc tgctagagaa gggggagcgg ttggcacagc cccagatctg 3000 cacaattgat gtctacatgg tgatggtcaa gtgttggatg attgatgaga 3050 acattcgccc aacctttaaa gaactagcca atgagttcac caggatggcc 3100 cgagacccac cacggtatct ggtcataaag agagagagtg ggcctggaat 3150 agcccctggg ccagagcccc atggtctgac aaacaagaag ctagaggaag 3200 tagagctgga gccagaacta gacctagacc tagacttgga agcagaggag 3250 gacaacctgg caaccaccac actgggctcc gccctcagcc taccagttgg 3300 aacacttaat cggccacgtg ggagccagag ccttttaagt ccatcatctg 3350 gatacatgcc catgaaccag ggtaatcttg gggagtcttg ccaggagtct 3400 gcagtttctg ggagcagtga acggtgcccc cgtccagtct ctctacaccc 3450 aatgccacgg ggatgcctgg catcagagtc atcagagggg catgtaacag 3500 gctctgaggc tgagctccag gagaaagtgt caatgtgtag gagccggagc 3550 aggagccgga gcccacggcc acgcggagat agcgcctacc attcccagcg 3600 ccacagtctg ctgactcctg ttaccccact ctccccaccc gggttagagg 3650 aagaggatgt caacggttat gtcatgccag atacacacct caaaggtact 3700 ccctcctccc gggaaggcac cctttcttca gtgggtctca gttctgtcct 3750 gggtactgaa gaagaagatg aagatgagga gtatgaatac atgaaccgga 3800 ggagaaggca cagtccacct catcccccta ggccaagttc ccttgaggag 3850 ctgggttatg agtacatgga tgtggggtca gacctcagtg cctctctggg 3900 cagcacacag agttgcccac tccaccctgt acccatcatg cccactgcag 3950 gcacaactcc agatgaagac tatgaatata tgaatcggca acgagatgga 4000 ggtggtcctg ggggtgatta tgcagccatg ggggcctgcc cagcatctga 4050 gcaagggtat gaagagatga gagcttttca ggggcctgga catcaggccc 4100 cccatgtcca ttatgcccgc ctaaaaactc tacgtagctt agaggctaca 4150 gactctgcct ttgataaccc tgattactgg catagcaggc ttttccccaa 4200 ggctaatgcc cagagaacgt aactcctgct ccctgtggca ctcagggagc 4250 atttaatggc agctagtgcc tttagagggt accgtcttct ccctattccc 4300 tctctctccc aggtcccagc cccttttccc cagtcccaga caattccatt 4350 caatctttgg aggcttttaa acattttgac acaaaattct tatggtatgt 4400 agccagctgt gcactttctt ctctttccca accccaggaa aggttttcct 4450 tattttgtgt gctttcccag tcccattcct cagcttcttc acaggcactc 4500 ctggagatat gaaggattac tctccatatc ccttcctctc aggctcttga 4550 ctacttggaa ctaggctctt atgtgtgcct ttgtttccca tcagactgtc 4600 aagaagagga aagggaggaa acctagcaga ggaaagtgta attttggttt 4650 atgactctta accccctaga aagacagaag cttaaaatct gtgaagaaag 4700 aggttaggag tagatattga ttactatcat aattcagcac ttaactatga 4750 gccaggcatc atactaaact tcacctacat tatctcactt agtcctttat 4800 catccttaaa acaattctgt gacatacata ttatctcatt ttacacaaag 4850 ggaagtcggg catggtggct catgcctgta atctcagcac tttgggaggc 4900 tgaggcagaa ggattacctg aggcaaggag tttgagacca gcttagccaa 4950 catagtaaga cccccatctc tttaaaaaaa aaaaaaaaaa aaaaaaaaaa 5000 actttagaac tgggtgcagt ggctcatgcc tgtaatccca gccagcactt 5050 tgggaggctg agatgggaag atcacttgag cccagaatta gagataagcc 5100 tatggaaaca tagcaagaca ctgtctctac aggggaaaaa aaaaaaagaa 5150 actgagcctt aaagagatga aataaattaa gcagtagatc caggatgcaa 5200 aatcctccca attcctgtgc atgtgctctt attgtaaggt gccaagaaaa 5250 actgatttaa gttacagccc ttgtttaagg ggcactgttt cttgtttttg 5300 cactgaatca agtctaaccc caacagccac atcctcctat acctagacat 5350 ctcatctcag gaagtggtgg tgggggtagt cagaaggaaa aataactgga 5400 catctttgtg taaaccataa tccacatgtg ccgtaaatga tcttcactcc 5450 ttatccgagg gcaaattcac aaggatcccc aagatccact tttagaagcc 5500 attctcatcc a 5511 tgtgagcctt gtgggggact atgtcccaaa gcctgtgagg gaacaggctc 1200 tgggagccgc ttccagactg tggactcgag caacattgat ggatttgtga 1250 actgcaccaa gatcctgggc aacctggact ttctgatcac cggcctcaat 1300 ggagacccct ggcacaagat ccctgccctg gacccagaga agctcaatgt 1350 gtacgggaga cttccggaca tcacaggtta cctgaacatc cagtcctggc 1400 cgccccacat gcacaacttc agtgtttttt ccaatttgac aaccattgga 1450 ggcagaagcc tctacaaccg gggcttctca ttgttgatca tgaagaactt 1500 gaatgtcaca tctctgggct tccgatccct gaaggaaatt agtgctgggc 1550 gtatctatat aagtgccaat aggcagctct gctaccacca ctctttgaac 1600 tggaccaagg tgcttcgggg gcctacggaa gagcgactag acatcaagca 1650 taatcggccg cgcagagact gcgtggcaga gggcaaagtg tgtgacccac 1700 tgtgctcctc tgggggatgc tggggcccag gccctggtca gtgcttgtcc 1750 tgtcgaaatt atagccgagg aggtgtctgt gtgacccact gcaactttct 1800 gaatggggag cctcgagaat ttgcccatga ggccgaatgc ttctcctgcc 1850 acccggaatg ccaacccatg gagggcactg ccacatgcaa tggctcgggc 1900 tctgatactt gtgctcaatg tgcccatttt cgagatgggc cccactgtgt 1950 gagcagctgc ccccatggag aka taggtgc caagggccca atctacaagt 2000 acccagatgt tcagaatgaa tgtcggccct gccatgagaa ctgcacccag 2050 gggtgtaaag gaccagagct tcaagactgt ttaggacaaa cactggtgct 2100 acccatctga gatcggcaaa caatggcttt gacagtgata gcaggattgg 2150 tagtgatttt catgatgctg ggcggcactt ttctctactg gcgtgggcgc 2200 cggattcaga ataaaagggc tatgaggcga tacttggaac ggggtgagag 2250 catagagcct ctggacccca gtgagaaggc taacaaagtc ttggccagaa 2300 gacagagcta tcttcaaaga aggaagctta aagtgcttgg ctcgggtgtc 2350 tttggaactg tgcacaaagg agtgtggatc cctgagggtg aatcaatcaa 2400 gattccagtc tgcattaaag tcattgagga caagagtgga cggcagagtt 2450 ttcaagctgt gacagatcat atgctggcca ttggcagcct ggaccatgcc 2500 cacattgtaa ggctgctggg actatgccca gggtcatctc tgcagcttgt 2550 cactcaatat ttgcctctgg gttctctgct ggatcatgtg agacaacacc 2600 ggggggcact ggggccacag ctgctgctca actggggagt acaaattgcc 2650 actaccttga aagggaatgt atggtgcata ggaacatggt gaaacctggc 2700 tgcccgaaac gtgctactca agtcacccag tcaggttcag gtggcagatt 2750 ttggtgtggc tgacctgctg cctcctgatg ataagcagct gctata CAGT 2800 ctccaattaa gaggccaaga gtggatggcc cttgagagta tccactttgg 2850 gaaatacaca caccagagtg atgtctggag ctatggtgtg acagtttggg 2900 agttgatgac cttcggggca gagccctatg cagggctacg attggctgaa 2950 gtaccagacc tgctagagaa gggggagcgg ttggcacagc cccagatctg 3000 cacaattgat gtctacatgg tgatggtcaa gtgttggatg attgatgaga 3050 aacctttaaa acattcgccc gaactagcca atgagttcac caggatggcc 3100 cgagacccac cacggtatct ggtcataaag agagagagtg ggcctggaat 3150 agcccctggg ccagagcccc atggtctgac aaacaagaag ctagaggaag 3200 tagagctgga gccagaacta gacctagacc tagacttgga agcagaggag 3250 gacaacctgg caaccaccac actgggctcc gccctcagcc taccagttgg 3300 aacacttaat cggccacgtg ggagccagag ccttttaagt ccatcatctg 3350 gatacatgcc catgaaccag ggtaatcttg gggagtcttg ccaggagtct 3400 gcagtttctg ggagcagtga acggtgcccc cgtccagtct ctctacaccc 3450 aatgccacgg ggatgcctgg catcagagtc atcagagggg catgtaacag 3500 gctctgaggc tgagctccag gagaaagtgt caatgtgtag gagccggagc 3550 aggagccgga gcccacggcc acgcggagat agcgcctacc attcccagcg 3600 ccacagtctg ctg actcctg ttaccccact ctccccaccc gggttagagg 3650 aagaggatgt caacggttat gtcatgccag atacacacct caaaggtact 3700 ccctcctccc gggaaggcac gtgggtctca cctttcttca gttctgtcct 3750 gaagaagatg gggtactgaa aagatgagga gtatgaatac atgaaccgga 3800 ggagaaggca cagtccacct catcccccta ggccaagttc ccttgaggag 3850 agtacatgga ctgggttatg tgtggggtca gacctcagtg cctctctggg 3900 cagcacacag agttgcccac tccaccctgt acccatcatg cccactgcag 3950 gcacaactcc agatgaagac tatgaatata tgaatcggca acgagatgga 4000 ggtggtcctg ggggtgatta tgcagccatg ggggcctgcc cagcatctga 4050 gaagagatga gcaagggtat gagcttttca ggggcctgga catcaggccc 4100 cccatgtcca ttatgcccgc ctaaaaactc tacgtagctt agaggctaca 4150 gactctgcct ttgataaccc tgattactgg catagcaggc ttttccccaa 4200 ggctaatgcc cagagaacgt aactcctgct ccctgtggca ctcagggagc 4250 atttaatggc agctagtgcc tttagagggt accgtcttct ccctattccc 4300 tctctctccc aggtcccagc cccttttccc cagtcccaga caattccatt 4350 caatctttgg aggcttttaa acattttgac acaaaattct tatggtatgt 4400 agccagctgt gcactttctt ctctttccca CACS aggaa aggttttcct 4450 tattttgtgt gctttcccag tcccattcct cagcttcttc acaggcactc 4500 ctggagatat gaaggattac tctccatatc ccttcctctc aggctcttga 4550 ctacttggaa ctaggctctt atgtgtgcct ttgtttccca tcagactgtc 4600 aagggaggaa aagaagagga ggaaagtgta acctagcaga attttggttt 4650 accccctaga atgactctta aagacagaag cttaaaatct gtgaagaaag 4700 aggttaggag tagatattga ttactatcat aattcagcac ttaactatga 4750 gccaggcatc atactaaact tcacctacat tatctcactt agtcctttat 4800 acaattctgt catccttaaa gacatacata ttatctcatt ttacacaaag 4850 ggaagtcggg catggtggct catgcctgta atctcagcac tttgggaggc 4900 tgaggcagaa ggattacctg aggcaaggag tttgagacca gcttagccaa 4950 cccccatctc catagtaaga aaaaaaaaaa tttaaaaaaa aaaaaaaaaa 5000 actttagaac tgggtgcagt ggctcatgcc tgtaatccca gccagcactt 5050 tgggaggctg agatgggaag atcacttgag cccagaatta gagataagcc 5100 tagcaagaca tatggaaaca ctgtctctac aggggaaaaa aaaaaaagaa 5150 aaagagatga actgagcctt aataaattaa gcagtagatc caggatgcaa 5200 aatcctccca attcctgtgc atgtgctctt attgtaaggt gccaagaaaa 5250 ctgatttaa gttacagccc ttgtttaagg ggcactgttt cttgtttttg 5300 cactgaatca agtctaaccc caacagccac atcctcctat acctagacat 5350 ctcatctcag gaagtggtgg tgggggtagt cagaaggaaa aataactgga 5400 catctttgtg taaaccataa tccacatgtg ccgtaaatga tcttcactcc 5450 ttatccgagg gcaaattcac aaggatcccc aagatccact tttagaagcc attctcatcc 5500 to 5511

<210> 24 <210> 24

<211> 5484 <211> 5484

<212> ADN <212> DNA

<213> Homo sapiens <213> Homo sapiens

<400> 24 <400> 24

aattgtcagc acgggatctg agacttccaa aaaatgaagc cggcgacagg 50 aattgtcagc acgggatctg agacttccaa aaaatgaagc cggcgacagg 50

actttgggtc tgggtgagcc ttctcgtggc ggcggggacc gtccagccca 100 actttgggtc tgggtgagcc ttctcgtggc ggcggggacc gtccagccca 100

gcgattctca gtcagtgtgt gcaggaacgg agaataaact gagctctctc 150 gcgattctca gtcagtgtgt gcaggaacgg agaataaact gagctctctc 150

tctgacctgg aacagcagta ccgagccttg cgcaagtact atgaaaactg 200 tctgacctgg aacagcagta ccgagccttg cgcaagtact atgaaaactg 200

tgaggttgtc atgggcaacc tggagataac cagcattgag cacaaccggg 250 tgaggttgtc atgggcaacc tggagataac cagcattgag cacaaccggg 250

acctctcctt cctgcggtct gttcgagaag tcacaggcta cgtgttagtg 300 acctctcctt cctgcggtct gttcgagaag tcacaggcta cgtgttagtg 300

gctcttaatc agtttcgtta cctgcctctg gagaatttac gcattattcg 350 gctcttaatc agtttcgtta cctgcctctg gagaatttac gcattattcg 350

tgggacaaaa ctttatgagg atcgatatgc cttggcaata tttttaaact 400 tgggacaaaa ctttatgagg atcgatatgc cttggcaata tttttaaact 400

acagaaaaga tggaaacttt ggacttcaag aacttggatt aaagaacttg 450 acagaaaaga tggaaacttt ggacttcaag aacttggatt aaagaacttg 450

acagaaatcc taaatggtgg agtctatgta gaccagaaca aattcctttg 500 acagaaatcc taaatggtgg agtctatgta gaccagaaca aattcctttg 500

ttatgcagac accattcatt ggcaagatat tgttcggaac ccatggcctt 550 ttatgcagac accattcatt ggcaagatat tgttcggaac ccatggcctt 550

ccaacttgac tcttgtgtca acaaatggta gttcaggatg tggacgttgc 600 cataagtcct gtactggccg ttgctgggga cccacagaaa atcattgcca 650 gactttgaca aggacggtgt gtgcagaaca atgtgacggc agatgctacg 700 gaccttacgt cagtgactgc tgccatcgag aatgtgctgg aggctgctca 750 ggacctaagg acacagactg ctttgcctgc atgaatttca atgacagtgg 800 agcatgtgtt actcagtgtc cccaaacctt tgtctacaat ccaaccacct 850 ttcaactgga gcacaatttc aatgcaaagt acacatatgg agcattctgt 900 gtcaagaaat gtccacataa ctttgtggta gattccagtt cttgtgtgcg 950 tgcctgccct agttccaaga tggaagtaga agaaaatggg attaaaatgt 1000 gtaaaccttg cactgacatt tgcccaaaag cttgtgatgg cattggcaca 1050 ggatcattga tgtcagctca gactgtggat tccagtaaca ttgacaaatt 1100 cataaactgt accaagatca atgggaattt gatctttcta gtcactggta 1150 ttcatgggga cccttacaat gcaattgaag ccatagaccc agagaaactg 1200 aacgtctttc ggacagtcag agagataaca ggtttcctga acatacagtc 1250 atggccacca aacatgactg acttcagtgt tttttctaac ctggtgacca 1300 ttggtggaag agtactctat agtggcctgt ccttgcttat cctcaagcaa 1350 cagggcatca cctctctaca gttccagtcc ctgaaggaaa tcagcgcagg 1400 aaacatctat attactgaca acagcaacct gtgttattat cataccatta 1450 actggacaac actcttcagc acaatcaacc agagaatagt aatccgggac 1500 aacagaaaag ctgaaaattg tactgctgaa ggaatggtgt gcaaccatct 1550 gtgttccagt gatggctgtt ggggacctgg gccagaccaa tgtctgtcgt 1600 gtcgccgctt cagtagagga aggatctgca tagagtcttg taacctctat 1650 gatggtgaat ttcgggagtt tgagaatggc tccatctgtg tggagtgtga 1700 cccccagtgt gagaagatgg aagatggcct cctcacatgc catggaccgg 1750 gtcctgacaa ctgtacaaag tgctctcatt ttaaagatgg cccaaactgt 1800 gtggaaaaat gtccagatgg cttacagggg gcaaacagtt tcattttcaa 1850 gtatgctgat ccagatcggg agtgccaccc atgccatcca aactgcaccc 1900 aagggtgtaa cggtcccact agtcatgact gcatttacta cccatggacg 1950 ggccattcca ctttaccaca acatgctaga actcccctga ttgcagctgg 2000 agtaattggt gggctcttca ttctggtcat tgtgggtctg acatttgctg 2050 tttatgttag aaggaagagc atcaaaaaga aaagagcctt gagaagattc 2100 ttggaaacag agttggtgga accattaact cccagtggca cagcacccaa 2150 tcaagctcaa cttcgtattt tgaaagaaac tgagctgaag agggtaaaag 2200 tccttggctc aggtgctttt ggaacggttt ataaaggtat ttgggtacct 2250 gaaggagaaa ctgtgaagat tcctgtggct attaagattc ttaatgagac 2300 aactggtccc aaggcaaatg tggagttcat ggatgaagct ctgatcatgg 2350 caagtatgga tcatccacac ctagtccggt tgctgggtgt gtgtctgagc 2400 ccaaccatcc agctggttac tcaacttatg ccccatggct gcctgttgga 2450 gtatgtccac gagcacaagg ataacattgg atcacaactg ctgcttaact 2500 ggtgtgtcca gatagctaag ggaatgatgt acctggaaga aagacgactc 2550 gttcatcggg atttggcagc ccgtaatgtc ttagtgaaat ctccaaacca 2600 tgtgaaaatc acagattttg ggctagccag actcttggaa ggagatgaaa 2650 aagagtacaa tgctgatgga ggaaagatgc caattaaatg gatggctctg 2700 gagtgtatac attacaggaa attcacccat cagagtgacg tttggagcta 2750 tggagttact atatgggaac tgatgacctt tggaggaaaa ccctatgatg 2800 gaattccaac gcgagaaatc cctgatttat tagagaaagg agaacgtttg 2850 cctcagcctc ccatctgcac tattgacgtt tacatggtca tggtcaaatg 2900 ttggatgatt gatgctgaca gtagacctaa atttaaggaa ctggctgctg 2950 agttttcaag gatggctcga gaccctcaaa gatacctagt tattcagggt 3000 gatgatcgta tgaagcttcc cagtccaaat gacagcaagt tctttcagaa 3050 tctcttggat gaagaggatt tggaagatat gatggatgct gaggagtact 3100 tggtccctca ggctttcaac atcccacctc ccatctatac ttccagagca 3150 agaattgact cgaataggag tgaaattgga cacagccctc ctcctgccta 3200 cacccccatg tcaggaaacc agtttgtata ccgagatgga ggttttgctg 3250 ctgaacaagg agtgtctgtg ccctacagag ccccaactag cacaattcca 3300 gaagctcctg tggcacaggg tgctactgct gagatttttg atgactcctg 3350 ctgtaatggc accctacgca agccagtggc accccatgtc caagaggaca 3400 gtagcaccca gaggtacagt gctgacccca ccgtgtttgc cccagaacgg 3450 agcccacgag gagagctgga tgaggaaggt tacatgactc ctatgcgaga 3500 caaacccaaa caagaatacc tgaatccagt ggaggagaac ccttttgttt 3550 ctcggagaaa aaatggagac cttcaagcat tggataatcc cgaatatcac 3600 aatgcatcca atggtccacc caaggccgag gatgagtatg tgaatgagcc 3650 actgtacctc aacacctttg ccaacacctt gggaaaagct gagtacctga 3700 agaacaacat actgtcaatg ccagagaagg ccaagaaagc gtttgacaac 3750 cctgactact ggaaccacag cctgccacct cggagcaccc ttcagcaccc 3800 agactacctg caggagtaca gcacaaaata tttttataaa cagaatgggc 3850 ggatccggcc tattgtggca gagaatcctg aatacctctc tgagttctcc 3900 ctgaagccag gcactgtgct gccgcctcca ccttacagac accggaatac 3950 tgtggtgtaa gctcagttgt ggttttttag gtggagagac acacctgctc 4000 caatttcccc acccccctct ctttctctgg tggtcttcct tctaccccaa 4050 ggccagtagt tttgacactt cccagtggaa gatacagaga tgcaatgata 4100 gttatgtgct tacctaactt gaacattaga gggaaagact gaaagagaaa 4150 gataggagga accacaatgt ttcttcattt ctctgcatgg gttggtcagg 4200 agaatgaaac agctagagaa ggaccagaaa atgtaaggca atgctgccta 4250 ctatcaaact agctgtcact ttttttcttt ttctttttct ttctttgttt 4300 ctttcttcct cttctttttt tttttttttt taaagcagat ggttgaaaca 4350 cccatgctat ctgttcctat ctgcaggaac tgatgtgtgc atatttagca 4400 tccctggaaa tcataataaa gtttccatta gaacaaaaga ataacatttt 4450 ctataacata tgatagtgtc tgaaattgag aatccagttt ctttccccag 4500 cagtttctgt cctagcaagt aagaatggcc aactcaactt tcataattta 4550 aaaatctcca ttaaagttat aactagtaat tatgttttca acactttttg 4600 gtttttttca ttttgttttg ctctgaccga ttcctttata tttgctcccc 4650 tatttttggc tttaatttct aattgcaaag atgtttacat caaagcttct 4700 tcacagaatt taagcaagaa atattttaat atagtgaaat ggccactact 4750 ttaagtatac aatctttaaa ataagaaagg gaggctaata tttttcatgc 4800 tatcaaatta tcttcaccct catcctttac atttttcaac attttttttt 4850 ctccataaat gacactactt gataggccgt tggttgtctg aagagtagaa 4900 gggaaactaa gagacagttc tctgtggttc aggaaaacta ctgatacttt 4950 caggggtggc ccaatgaggg aatccattga actggaagaa acacactgga 5000 ttgggtatgt ctacctggca gatactcaga aatgtagttt gcacttaagc 5050 tgtaatttta tttgttcttt ttctgaactc cattttggat tttgaatcaa 5100 gcaatatgga agcaaccagc aaattaacta atttaagtac atttttaaaa 5150 aaagagctaa gataaagact gtggaaatgc caaaccaagc aaattaggaa 5200 ccttgcaacg gtatccaggg actatgatga gaggccagca cattatcttc 5250 atatgtcacc tttgctacgc aaggaaattt gttcagttcg tatacttcgt 5300 aagaaggaat gcgagtaagg attggcttga attccatgga atttctagta 5350 tgagactatt tatatgaagt agaaggtaac tctttgcaca taaattggta 5400 taataaaaag aaaaacacaa acattcaaag cttagggata ggtccttggg 5450 tcaaaagttg taaataaatg tgaaacatct tctc 5484 ccaacttgac acaaatggta tcttgtgtca gttcaggatg tggacgttgc 600 cataagtcct gtactggccg ttgctgggga atcattgcca cccacagaaa 650 gactttgaca aggacggtgt gtgcagaaca atgtgacggc agatgctacg 700 gaccttacgt cagtgactgc tgccatcgag aatgtgctgg aggctgctca 750 ggacctaagg acacagactg ctttgcctgc atgaatttca atgacagtgg 800 agcatgtgtt actcagtgtc cccaaacctt tgtctacaat ccaaccacct 850 ttcaactgga gcacaatttc aatgcaaagt acacatatgg agcattctgt 900 gtccacataa gtcaagaaat ctttgtggta gattccagtt cttgtgtgcg 950 agttccaaga tgcctgccct tggaagtaga agaaaatggg attaaaatgt 1000 gtaaaccttg cactgacatt tgcccaaaag cttgtgatgg cattggcaca 1050 tgtcagctca ggatcattga gactgtggat tccagtaaca ttgacaaatt 1100 accaagatca cataaactgt atgggaattt gatctttcta gtcactggta 1150 ttcatgggga cccttacaat gcaattgaag ccatagaccc agagaaactg 1200 aacgtctttc ggacagtcag agagataaca ggtttcctga acatacagtc 1250 atggccacca aacatgactg acttcagtgt tttttctaac ctggtgacca 1300 ttggtggaag agtactctat agtggcctgt ccttgcttat cctcaagcaa 1350 cctctctaca cagggcatca gttccagtcc ctgaaggaaa tcagcgcagg 1400 aaacatctat attactgaca acagcaacct gtgttattat cataccatta 1450 actggacaac actcttcagc acaatcaacc agagaatagt aatccgggac 1500 aacagaaaag ctgaaaattg tactgctgaa ggaatggtgt gcaaccatct 1550 gtgttccagt gatggctgtt ggggacctgg gccagaccaa tgtctgtcgt 1600 cagtagagga gtcgccgctt aggatctgca tagagtcttg taacctctat 1650 gatggtgaat ttcgggagtt tgagaatggc tccatctgtg tggagtgtga 1700 cccccagtgt gagaagatgg aagatggcct cctcacatgc catggaccgg 1750 gtcctgacaa ctgtacaaag tgctctcatt ttaaagatgg cccaaactgt 1800 gtggaaaaat gtccagatgg cttacagggg gcaaacagtt tcattttcaa 1850 gtatgctgat ccagatcggg agtgccaccc atgccatcca aactgcaccc 1900 aagggtgtaa cggtcccact agtcatgact gcatttacta cccatggacg 1950 ctttaccaca ggccattcca acatgctaga actcccctga ttgcagctgg 2000 agtaattggt gggctcttca ttctggtcat tgtgggtctg acatttgctg 2050 tttatgttag aaggaagagc atcaaaaaga aaagagcctt gagaagattc 2100 agttggtgga ttggaaacag accattaact cccagtggca cagcacccaa tcaagctcaa 2150 cttcgtattt tgaaagaaac tgagctgaag agggtaaaag 22 00 tccttggctc aggtgctttt ggaacggttt ataaaggtat ttgggtacct 2250 gaaggagaaa ctgtgaagat tcctgtggct attaagattc ttaatgagac 2300 aactggtccc aaggcaaatg tggagttcat ggatgaagct ctgatcatgg 2350 caagtatgga tcatccacac ctagtccggt tgctgggtgt gtgtctgagc 2400 ccaaccatcc agctggttac tcaacttatg ccccatggct gcctgttgga 2450 gtatgtccac gagcacaagg ataacattgg atcacaactg ctgcttaact 2500 ggtgtgtcca gatagctaag ggaatgatgt acctggaaga aagacgactc 2550 gttcatcggg atttggcagc ccgtaatgtc ttagtgaaat ctccaaacca 2600 tgtgaaaatc acagattttg ggctagccag actcttggaa ggagatgaaa 2650 tgctgatgga aagagtacaa ggaaagatgc caattaaatg gatggctctg 2700 gagtgtatac attacaggaa attcacccat cagagtgacg tttggagcta 2750 tggagttact atatgggaac tgatgacctt tggaggaaaa ccctatgatg 2800 gaattccaac gcgagaaatc cctgatttat tagagaaagg agaacgtttg 2850 cctcagcctc ccatctgcac tattgacgtt tacatggtca tggtcaaatg 2900 gatgctgaca ttggatgatt atttaaggaa gtagacctaa ctggctgctg 2950 gatggctcga agttttcaag gaccctcaaa gatacctagt tattcagggt 3000 gatgatcgta tgaagcttcc cagtccaaat gacagcaagt tctttcagaa 3050 tctcttggat gaagaggatt tggaagatat gatggatgct gaggagtact 3100 tggtccctca ggctttcaac atcccacctc ccatctatac ttccagagca 3150 agaattgact cgaataggag tgaaattgga ctcctgccta cacagccctc 3200 cacccccatg tcaggaaacc agtttgtata ccgagatgga ggttttgctg 3250 ctgaacaagg agtgtctgtg ccctacagag ccccaactag cacaattcca 3300 gaagctcctg tggcacaggg tgctactgct gagatttttg atgactcctg 3350 ctgtaatggc accctacgca agccagtggc accccatgtc caagaggaca 3400 gtagcaccca gaggtacagt gctgacccca ccgtgtttgc cccagaacgg 3450 agcccacgag gagagctgga tgaggaaggt tacatgactc ctatgcgaga 3500 caaacccaaa caagaatacc tgaatccagt ggaggagaac ccttttgttt 3550 ctcggagaaa aaatggagac cttcaagcat tggataatcc cgaatatcac 3600 aatgcatcca atggtccacc caaggccgag gatgagtatg tgaatgagcc 3650 actgtacctc aacacctttg ccaacacctt gggaaaagct gagtacctga 3700 agaacaacat actgtcaatg ccagagaagg ccaagaaagc gtttgacaac 3750 cctgactact ggaaccacag cctgccacct cggagcaccc ttcagcaccc 3800 agactacctg caggagtaca tttttataaa gcacaaaata c agaatgggc 3850 ggatccggcc tattgtggca gagaatcctg aatacctctc tgagttctcc 3900 ctgaagccag gcactgtgct gccgcctcca ccttacagac accggaatac 3950 tgtggtgtaa gctcagttgt ggttttttag gtggagagac acacctgctc 4000 caatttcccc acccccctct ctttctctgg tggtcttcct tctaccccaa 4050 ggccagtagt tttgacactt cccagtggaa gatacagaga tgcaatgata 4100 gttatgtgct tacctaactt gaacattaga gggaaagact gaaagagaaa 4150 gataggagga accacaatgt ttcttcattt ctctgcatgg gttggtcagg 4200 agctagagaa agaatgaaac ggaccagaaa atgtaaggca atgctgccta 4250 ctatcaaact agctgtcact ttttttcttt ttctttttct ttctttgttt 4300 ctttcttcct cttctttttt tttttttttt taaagcagat ggttgaaaca 4350 cccatgctat ctgttcctat ctgcaggaac tgatgtgtgc atatttagca 4400 tcataataaa tccctggaaa gtttccatta gaacaaaaga ataacatttt 4450 ctataacata tgatagtgtc tgaaattgag aatccagttt ctttccccag 4500 cagtttctgt cctagcaagt aagaatggcc aactcaactt tcataattta 4550 aaaatctcca ttaaagttat aactagtaat tatgttttca acactttttg 4600 ttttgttttg gtttttttca ctctgaccga ttcctttata tttgctcccc 4650 tatttttg gc tttaatttct aattgcaaag atgtttacat caaagcttct 4700 tcacagaatt taagcaagaa atattttaat atagtgaaat ggccactact 4750 ttaagtatac aatctttaaa ataagaaagg gaggctaata tttttcatgc 4800 tatcaaatta tcttcaccct catcctttac atttttcaac attttttttt 4850 ctccataaat gacactactt gataggccgt tggttgtctg aagagtagaa 4900 gggaaactaa gagacagttc tctgtggttc aggaaaacta ctgatacttt 4950 ccaatgaggg caggggtggc actggaagaa aatccattga acacactgga 5000 ctacctggca ttgggtatgt gatactcaga aatgtagttt gcacttaagc 5050 tgtaatttta tttgttcttt ttctgaactc cattttggat tttgaatcaa 5100 gcaatatgga agcaaccagc aaattaacta atttaagtac atttttaaaa 5150 aaagagctaa gataaagact gtggaaatgc caaaccaagc aaattaggaa 5200 ccttgcaacg gtatccaggg gaggccagca actatgatga cattatcttc 5250 atatgtcacc tttgctacgc aaggaaattt gttcagttcg tatacttcgt 5300 aagaaggaat gcgagtaagg attggcttga atttctagta attccatgga 5350 tgagactatt tatatgaagt agaaggtaac tctttgcaca taaattggta 5400 taataaaaag aaaaacacaa acattcaaag cttagggata ggtccttggg 5450 tcaaaagttg taaataaatg tgaaacatct tctc 5484

<210> 25 <210> 25

<211> 4093 <211> 4093

<212> ADN <212> DNA

<213> Homo sapiens <213> Homo sapiens

<400> 25 <400> 25

cgcgcgctgc ctgaggacgc cgcggccccc gcccccgcca tgggcgcccc 50 tgcctgcgcc ctcgcgctct gcgtggccgt ggccatcgtg gccggcgcct 100 cctcggagtc cttggggacg gagcagcgcg tcgtggggcg agcggcagaa 150 gtcccgggcc cagagcccgg ccagcaggag cagttggtct tcggcagcgg 200 ggatgctgtg gagctgagct gtcccccgcc cgggggtggt cccatggggc 250 ccactgtctg ggtcaaggat ggcacagggc tggtgccctc ggagcgtgtc 300 ctggtggggc cccagcggct gcaggtgctg aatgcctccc acgaggactc 350 cggggcctac agctgccggc agcggctcac gcagcgcgta ctgtgccact 400 tcagtgtgcg ggtgacagac gctccatcct cgggagatga cgaagacggg 450 gaggacgagg ctgaggacac aggtgtggac acaggggccc cttactggac 500 acggcccgag cggatggaca agaagctgct ggccgtgccg gccgccaaca 550 ccgtccgctt ccgctgccca gccgctggca accccactcc ctccatctcc 600 tggctgaaga acggcaggga gttccgcggc gagcaccgca ttggaggcat 650 caagctgcgg catcagcagt ggagcctggt catggaaagc gtggtgccct 700 cggaccgcgg caactacacc tgcgtcgtgg agaacaagtt tggcagcatc 750 cggcagacgt acacgctgga cgtgctggag cgctccccgc accggcccat 800 cctgcaggcg gggctgccgg ccaaccagac ggcggtgctg ggcagcgacg 850 tggagttcca ctgcaaggtg tacagtgacg cacagcccca catccagtgg 900 ctcaagcacg tggaggtgaa cggcagcaag gtgggcccgg acggcacacc 950 ctacgttacc gtgctcaaga cggcgggcgc taacaccacc gacaaggagc 1000 tagaggttct ctccttgcac aacgtcacct ttgaggacgc cggggagtac 1050 acctgcctgg cgggcaattc tattgggttt tctcatcact ctgcgtggct 1100 ggtggtgctg ccagccgagg aggagctggt ggaggctgac gaggcgggca 1150 gtgtgtatgc aggcatcctc agctacgggg tgggcttctt cctgttcatc 1200 ctggtggtgg cggctgtgac gctctgccgc ctgcgcagcc cccccaagaa 1250 aggcctgggc tcccccaccg tgcacaagat ctcccgcttc ccgctcaagc 1300 gacaggtgtc cctggagtcc aacgcgtcca tgagctccaa cacaccactg 1350 gtgcgcatcg caaggctgtc ctcaggggag ggccccacgc tggccaatgt 1400 ctccgagctc gagctgcctg ccgaccccaa atgggagctg tctcgggccc 1450 ggctgaccct gggcaagccc cttggggagg gctgcttcgg ccaggtggtc 1500 atggcggagg ccatcggcat tgacaaggac cgggccgcca agcctgtcac 1550 cgtagccgtg aagatgctga aagacgatgc cactgacaag gacctgtcgg 1600 acctggtgtc tgagatggag atgatgaaga tgatcgggaa acacaaaaac 1650 atcatcaacc tgctgggcgc ctgcacgcag ggcgggcccc tgtacgtgct 1700 ggtggagtac gcggccaagg gtaacctgcg ggagtttctg cgggcgcggc 1750 ggcccccggg cctggactac tccttcgaca cctgcaagcc gcccgaggag 1800 cagctcacct tcaaggacct ggtgtcctgt gcctaccagg tggcccgggg 1850 catggagtac ttggcctccc agaagtgcat ccacagggac ctggctgccc 1900 gcaatgtgct ggtgaccgag gacaacgtga tgaagatcgc agacttcggg 1950 ctggcccggg acgtgcacaa cctcgactac tacaagaaga caaccaacgg 2000 ccggctgccc gtgaagtgga tggcgcctga ggccttgttt gaccgagtct 2050 acactcacca gagtgacgtc tggtcctttg gggtcctgct ctgggagatc 2100 ttcacgctgg ggggctcccc gtaccccggc atccctgtgg aggagctctt 2150 caagctgctg aaggagggcc accgcatgga caagcccgcc aactgcacac 2200 acgacctgta catgatcatg cgggagtgct ggcatgccgc gccctcccag 2250 aggcccacct tcaagcagct ggtggaggac ctggaccgtg tccttaccgt 2300 gacgtccacc gacgagtacc tggacctgtc ggcgcctttc gagcagtact 2350 ccccgggtgg ccaggacacc cccagctcca gctcctcagg ggacgactcc 2400 gtgtttgccc acgacctgct gcccccggcc ccacccagca gtgggggctc 2450 gcggacgtga agggccactg gtccccaaca atgtgagggg tccctagcag 2500 ccctccctgc tgctggtgca cagccactcc ccggcatgag actcagtgca 2550 gatggagaga cagctacaca gagctttggt ctgtgtgtgt gtgtgtgcgt 2600 gtgtgtgtgt gtgtgcacat ccgcgtgtgc ctgtgtgcgt gcgcatcttg 2650 cctccaggtg cagaggtacc ctgggtgtcc ccgctgctgt gcaacggtct 2700 cctgactggt gctgcagcac cgaggggcct ttgttctggg gggacccagt 2750 gcagaatgta agtgggccca cccggtggga ccccgtgggg cagggagctg 2800 ggcccgacat ggctcggcct ctgcctttgc accacgggac atcacagggt 2850 gcgctcggcc cctcccacac ccaaagctga gcctgcaggg aagccccaca 2900 tgtccagcac cttgtgcctg gggtgttagt ggcaccgcct ccccacctcc 2950 aggctttccc acttcccacc ctgcccctca gagactgaaa ttacgggtac 3000 ctgaagatgg gagcctttac cttttatgca aaaggtttat tccggaaact 3050 agtgtacatt tctataaata gatgctgtgt atatggtata tatacatata 3100 tatatataac atatatggaa gaggaaaagg ctggtacaac ggaggcctgc 3150 gaccctgggg gcacaggagg caggcatggc cctgggcggg gcgtgggggg 3200 gcgtggaggg aggccccagg ggtctcaccc atgcaagcag aggaccaggg 3250 ctttttctgg caccgcagtt ttgttttaaa actggacctg tatatttgta 3300 aagctattta tgggcccctg gcactcttgt tcccacaccc caacacttcc 3350 agcatttagc tggccacatg gcggagagtt ttaattttta acttattgac 3400 aaccgagaag gtttatcccg ccgatagagg gacggccaag aatgtacgtc 3450 cagcctgccc cggagctgga ggatcccctc caagcctaaa aggttgttaa 3500 tagttggagg tgattccagt gaagatattt tatttgcttt gtcctttttc 3550 aggagaatta gatttctata ggatttttct ttaggagatt tattttttgg 3600 acttcaaagc aagctggtat tttcatacaa attcttctaa ttgctgtgtg 3650 tcccaggcag ggagacggtt tccagggagg ggccggccct gtgtgcaggt 3700 tccgatgtta ttagatgtta caagtttata tatatctata tatataattt 3750 attgagtttt tacaagatgt atttgttgta gacttaacac ttcttacgca 3800 atgcttctag agttttatag cctggactgc tacctttcaa agcttggagg 3850 gaagccgtga attcagttgg ttcgttctgt actgttactg ggccctgagt 3900 ctgggcagct gtcccttgct tgcctgcagg gccatggctc agggtggtct 3950 cttcttgggg cccagtgcat ggtggccaga ggtgtcaccc aaaccggcag 4000 gtgcgatttt gttaacccag cgacgaactt tccgaaaaat aaagacacct 4050 ggttgctaac ctgaaaaaaa aaaaaaaaaa aaaaaaaaaa aaa 4093 cgcgcgctgc ctgaggacgc cgcggccccc gcccccgcca tgggcgcccc 50 tgcctgcgcc ctcgcgctct gcgtggccgt ggccatcgtg gccggcgcct 100 cctcggagtc cttggggacg gagcagcgcg tcgtggggcg agcggcagaa 150 gtcccgggcc cagagcccgg ccagcaggag cagttggtct tcggcagcgg 200 ggatgctgtg gagctgagct gtcccccgcc cgggggtggt cccatggggc 250 ccactgtctg ggtcaaggat ggcacagggc tggtgccctc ggagcgtgtc 300 ctggtggggc cccagcggct gcaggtgctg aatgcctccc acgaggactc 350 cggggcctac agctgccggc agcggctcac gcagcgcgta ctgtgccact 400 tcagtgtgcg ggtgacagac gctccatcct cgggagatga cgaagacggg 450 gaggacgagg ctgaggacac aggtgtggac acaggggccc cttactggac 500 acggcccgag cggatggaca agaagctgct ggccgtgccg gccgccaaca 550 ccgctgccca ccgtccgctt gccgctggca accccactcc ctccatctcc 600 acggcaggga tggctgaaga gttccgcggc gagcaccgca ttggaggcat 650 caagctgcgg catcagcagt ggagcctggt catggaaagc gtggtgccct 700 cggaccgcgg caactacacc tgcgtcgtgg agaacaagtt tggcagcatc 750 cggcagacgt acacgctgga cgtgctggag cgctccccgc accggcccat 800 cctgcaggcg gggctgccgg ccaaccagac ggcggtgc tg ggcagcgacg 850 tggagttcca ctgcaaggtg tacagtgacg cacagcccca catccagtgg 900 ctcaagcacg tggaggtgaa cggcagcaag gtgggcccgg acggcacacc 950 ctacgttacc gtgctcaaga cggcgggcgc taacaccacc gacaaggagc 1000 tagaggttct ctccttgcac aacgtcacct ttgaggacgc cggggagtac 1050 acctgcctgg cgggcaattc tattgggttt tctcatcact ctgcgtggct 1100 ggtggtgctg ccagccgagg aggagctggt ggaggctgac gaggcgggca 1150 gtgtgtatgc aggcatcctc agctacgggg tgggcttctt cctgttcatc 1200 ctggtggtgg cggctgtgac gctctgccgc ctgcgcagcc cccccaagaa 1250 aggcctgggc tcccccaccg tgcacaagat ctcccgcttc ccgctcaagc 1300 gacaggtgtc cctggagtcc aacgcgtcca tgagctccaa cacaccactg 1350 gtgcgcatcg caaggctgtc ctcaggggag ggccccacgc tggccaatgt 1400 ctccgagctc gagctgcctg ccgaccccaa atgggagctg tctcgggccc 1450 ggctgaccct gggcaagccc cttggggagg gctgcttcgg ccaggtggtc 1500 atggcggagg ccatcggcat tgacaaggac cgggccgcca agcctgtcac 1550 cgtagccgtg aagatgctga aagacgatgc cactgacaag gacctgtcgg 1600 acctggtgtc tgagatggag atgatgaaga tgatcgggaa acacaaaaac 1650 atcatcaa cc tgctgggcgc ctgcacgcag ggcgggcccc tgtacgtgct 1700 ggtggagtac gcggccaagg gtaacctgcg ggagtttctg cgggcgcggc 1750 ggcccccggg cctggactac tccttcgaca cctgcaagcc gcccgaggag 1800 cagctcacct tcaaggacct ggtgtcctgt gcctaccagg tggcccgggg 1850 catggagtac ttggcctccc agaagtgcat ccacagggac ctggctgccc 1900 gcaatgtgct ggtgaccgag gacaacgtga tgaagatcgc agacttcggg 1950 ctggcccggg acgtgcacaa cctcgactac tacaagaaga caaccaacgg 2000 ccggctgccc gtgaagtgga tggcgcctga ggccttgttt gaccgagtct 2050 acactcacca gagtgacgtc tggtcctttg gggtcctgct ctgggagatc 2100 ttcacgctgg ggggctcccc gtaccccggc atccctgtgg aggagctctt 2150 caagctgctg aaggagggcc accgcatgga caagcccgcc aactgcacac 2200 acgacctgta catgatcatg cgggagtgct ggcatgccgc gccctcccag 2250 aggcccacct tcaagcagct ggtggaggac ctggaccgtg tccttaccgt 2300 gacgtccacc gacgagtacc tggacctgtc ggcgcctttc gagcagtact 2350 ccccgggtgg ccaggacacc cccagctcca gctcctcagg ggacgactcc 2400 gtgtttgccc acgacctgct gcccccggcc ccacccagca gtgggggctc 2450 agggccactg gcggacgtga gtccccaaca atgtgagggg tccctagcag 2500 tgctggtgca ccctccctgc ccggcatgag cagccactcc actcagtgca 2550 cagctacaca gatggagaga gagctttggt ctgtgtgtgt gtgtgtgcgt 2600 gtgtgtgtgt gtgtgcacat ccgcgtgtgc ctgtgtgcgt gcgcatcttg 2650 cctccaggtg cagaggtacc ctgggtgtcc ccgctgctgt gcaacggtct 2700 cctgactggt gctgcagcac cgaggggcct ttgttctggg gggacccagt 2750 agtgggccca gcagaatgta cccggtggga ccccgtgggg cagggagctg 2800 ggcccgacat ggctcggcct ctgcctttgc accacgggac atcacagggt 2850 gcgctcggcc cctcccacac ccaaagctga gcctgcaggg aagccccaca 2900 tgtccagcac cttgtgcctg gggtgttagt ggcaccgcct ccccacctcc 2950 aggctttccc acttcccacc ctgcccctca gagactgaaa ttacgggtac 3000 ctgaagatgg gagcctttac cttttatgca aaaggtttat tccggaaact 3050 tctataaata agtgtacatt atatggtata gatgctgtgt tatacatata 3100 tatatataac atatatggaa gaggaaaagg ctggtacaac ggaggcctgc 3150 gaccctgggg gcacaggagg caggcatggc cctgggcggg gcgtgggggg 3200 gcgtggaggg aggccccagg ggtctcaccc atgcaagcag aggaccaggg 3250 ctttttctgg caccgcagtt ttgttttaaa actggacctg tatatttgta 33 00 aagctattta tgggcccctg gcactcttgt tcccacaccc caacacttcc 3350 agcatttagc tggccacatg gcggagagtt ttaattttta acttattgac 3400 aaccgagaag gtttatcccg ccgatagagg gacggccaag aatgtacgtc 3450 cggagctgga cagcctgccc ggatcccctc caagcctaaa aggttgttaa 3500 tagttggagg tgattccagt gaagatattt tatttgcttt gtcctttttc 3550 gatttctata aggagaatta ggatttttct ttaggagatt tattttttgg 3600 acttcaaagc aagctggtat tttcatacaa attcttctaa ttgctgtgtg 3650 tcccaggcag ggagacggtt tccagggagg ggccggccct gtgtgcaggt 3700 tccgatgtta ttagatgtta tatatctata caagtttata tatataattt 3750 attgagtttt tacaagatgt atttgttgta gacttaacac ttcttacgca 3800 atgcttctag agttttatag cctggactgc tacctttcaa agcttggagg 3850 gaagccgtga attcagttgg ttcgttctgt actgttactg ggccctgagt 3900 ctgggcagct gtcccttgct tgcctgcagg gccatggctc agggtggtct 3950 cttcttgggg cccagtgcat ggtggccaga ggtgtcaccc aaaccggcag 4000 gtgcgatttt gttaacccag cgacgaactt tccgaaaaat aaagacacct aaaaaaaaaa aaaaaaaaaa 4050 ctgaaaaaaa ggttgctaac aaa 4093

<210> 26 <210> 26

<211> 8680 <211> 8680

<212> ADN <212> DNA

<213> Homo sapiens <213> Homo sapiens

<400> 26 <400> 26

acggggcctg aagcggcggt accggtgctg gcggcggcag ctgaggcctt 50 acggggcctg aagcggcggt accggtgctg gcggcggcag ctgaggcctt 50

ggccgaagcc gcgcgaacct cagggcaaga tgcttggaac cggacctgcc 100 ggccgaagcc gcgcgaacct cagggcaaga tgcttggaac cggacctgcc 100

gccgccacca ccgctgccac cacatctagc aatgtgagcg tcctgcagca 150 gccgccacca ccgctgccac cacatctagc aatgtgagcg tcctgcagca 150

gtttgccagt ggcctaaaga gccggaatga ggaaaccagg gccaaagccg 200 gtttgccagt ggcctaaaga gccggaatga ggaaaccagg gccaaagccg 200

ccaaggagct ccagcactat gtcaccatgg aactccgaga gatgagtcaa 250 ccaaggagct ccagcactat gtcaccatgg aactccgaga gatgagtcaa 250

gaggagtcta ctcgcttcta tgaccaactg aaccatcaca tttttgaatt 300 gaggagtcta ctcgcttcta tgaccaactg aaccatcaca tttttgaatt 300

ggtttccagc tcagatgcca atgagaggaa aggtggcatc ttggccatag 350 ggtttccagc tcagatgcca atgagaggaa aggtggcatc ttggccatag 350

ctagcctcat aggagtggaa ggtgggaatg ccacccgaat tggcagattt 400 ctagcctcat aggagtggaa ggtgggaatg ccacccgaat tggcagattt 400

gccaactatc ttcggaacct cctcccctcc aatgacccag ttgtcatgga 450 gccaactatc ttcggaacct cctcccctcc aatgacccag ttgtcatgga 450

aatggcatcc aaggccattg gccgtcttgc catggcaggg gacactttta 500 aatggcatcc aaggccattg gccgtcttgc catggcaggg gacactttta 500

ccgctgagta cgtggaattt gaggtgaagc gagccctgga atggctgggt 550 ccgctgagta cgtggaattt gaggtgaagc gagccctgga atggctgggt 550

gctgaccgca atgagggccg gagacatgca gctgtcctgg ttctccgtga 600 gctgaccgca atgagggccg gagacatgca gctgtcctgg ttctccgtga 600

gctggccatc agcgtcccta ccttcttctt ccagcaagtg caacccttct 650 gctggccatc agcgtcccta ccttcttctt ccagcaagtg caacccttct 650

ttgacaacat ttttgtggcc gtgtgggacc ccaaacaggc catccgtgag 700 ttgacaacat ttttgtggcc gtgtgggacc ccaaacaggc catccgtgag 700

ggagctgtag ccgcccttcg tgcctgtctg attctcacaa cccagcgtga 750 ggagctgtag ccgcccttcg tgcctgtctg attctcacaa cccagcgtga 750

gccgaaggag atgcagaagc ctcagtggta caggcacaca tttgaagaag 800 gccgaaggag atgcagaagc ctcagtggta caggcacaca tttgaagaag 800

cagagaaggg atttgatgag accttggcca aagagaaggg catgaatcgg 850 cagagaaggg atttgatgag accttggcca aagagaaggg catgaatcgg 850

gatgatcgga tccatggagc cttgttgatc cttaacgagc tggtccgaat 900 cagcagcatg gagggagagc gtctgagaga agaaatggaa gaaatcacac 950 agcagcagct ggtacacgac aagtactgca aagatctcat gggcttcgga 1000 acaaaacctc gtcacattac ccccttcacc agtttccagg ctgtacagcc 1050 ccagcagtca aatgccttgg tggggctgct ggggtacagc tctcaccaag 1100 gcctcatggg atttgggacc tcccccagtc cagctaagtc caccctggtg 1150 gagagccggt gttgcagaga cttgatggag gagaaatttg atcaggtgtg 1200 ccagtgggtg ctgaaatgca ggaatagcaa gaactcgctg atccaaatga 1250 caatccttaa tttgttgccc cgcttggctg cattccgacc ttctgccttc 1300 acagataccc agtatctcca agataccatg aaccatgtcc taagctgtgt 1350 caagaaggag aaggaacgta cagcggcctt ccaagccctg gggctacttt 1400 ctgtggctgt gaggtctgag tttaaggtct atttgcctcg cgtgctggac 1450 atcatccgag cggccctgcc cccaaaggac ttcgcccata agaggcagaa 1500 ggcaatgcag gtggatgcca cagtcttcac ttgcatcagc atgctggctc 1550 gagcaatggg gccaggcatc cagcaggata tcaaggagct gctggagccc 1600 atgctggcag tgggactaag ccctgccctc actgcagtgc tctacgacct 1650 gagccgtcag attccacagc taaagaagga cattcaagat gggctactga 1700 aaatgctgtc cctggtcctt atgcacaaac cccttcgcca cccaggcatg 1750 cccaagggcc tggcccatca gctggcctct cctggcctca cgaccctccc 1800 tgaggccagc gatgtgggca gcatcactct tgccctccga acgcttggca 1850 gctttgaatt tgaaggccac tctctgaccc aatttgttcg ccactgtgcg 1900 gatcatttcc tgaacagtga gcacaaggag atccgcatgg aggctgcccg 1950 cacctgctcc cgcctgctca caccctccat ccacctcatc agtggccatg 2000 ctcatgtggt tagccagacc gcagtgcaag tggtggcaga tgtgcttagc 2050 aaactgctcg tagttgggat aacagatcct gaccctgaca ttcgctactg 2100 tgtcttggcg tccctggacg agcgctttga tgcacacctg gcccaggcgg 2150 agaacttgca ggccttgttt gtggctctga atgaccaggt gtttgagatc 2200 cgggagctgg ccatctgcac tgtgggccga ctcagtagca tgaaccctgc 2250 ctttgtcatg cctttcctgc gcaagatgct catccagatt ttgacagagt 2300 tggagcacag tgggattgga agaatcaaag agcagagtgc ccgcatgctg 2350 gggcacctgg tctccaatgc cccccgactc atccgcccct acatggagcc 2400 tattctgaag gcattaattt tgaaactgaa agatccagac cctgatccaa 2450 acccaggtgt gatcaataat gtcctggcaa caataggaga attggcacag 2500 gttagtggcc tggaaatgag gaaatgggtt gatgaacttt ttattatcat 2550 catggacatg ctccaggatt cctctttgtt ggccaaaagg caggtggctc 2600 tgtggaccct gggacagttg gtggccagca ctggctatgt agtagagccc 2650 tacaggaagt accctacttt gcttgaggtg ctactgaatt ttctgaagac 2700 tgagcagaac cagggtacac gcagagaggc catccgtgtg ttagggcttt 2750 taggggcttt ggatccttac aagcacaaag tgaacattgg catgatagac 2800 cagtcccggg atgcctctgc tgtcagcctg tcagaatcca agtcaagtca 2850 ggattcctct gactatagca ctagtgaaat gctggtcaac atgggaaact 2900 tgcctctgga tgagttctac ccagctgtgt ccatggtggc cctgatgcgg 2950 atcttccgag accagtcact ctctcatcat cacaccatgg ttgtccaggc 3000 catcaccttc atcttcaagt ccctgggact caaatgtgtg cagttcctgc 3050 cccaggtcat gcccacgttc cttaacgtca ttcgagtctg tgatggggcc 3100 atccgggaat ttttgttcca gcagctggga atgttggtgt cctttgtgaa 3150 gagccacatc agaccttata tggatgaaat agtcaccctc atgagagaat 3200 tctgggtcat gaacacctca attcagagca cgatcattct tctcattgag 3250 caaattgtgg tagctcttgg gggtgaattt aagctctacc tgccccagct 3300 gatcccacac atgctgcgtg tcttcatgca tgacaacagc ccaggccgca 3350 ttgtctctat caagttactg gctgcaatcc agctgtttgg cgccaacctg 3400 gatgactacc tgcatttact gctgcctcct attgttaagt tgtttgatgc 3450 ccctgaagct ccactgccat ctcgaaaggc agcgctagag actgtggacc 3500 gcctgacgga gtccctggat ttcactgact atgcctcccg gatcattcac 3550 cctattgttc gaacactgga ccagagccca gaactgcgct ccacagccat 3600 ggacacgctg tcttcacttg tttttcagct ggggaagaag taccaaattt 3650 tcattccaat ggtgaataaa gttctggtgc gacaccgaat caatcatcag 3700 cgctatgatg tgctcatctg cagaattgtc aagggataca cacttgctga 3750 tgaagaggag gatcctttga tttaccagca tcggatgctt aggagtggcc 3800 aaggggatgc attggctagt ggaccagtgg aaacaggacc catgaagaaa 3850 ctgcacgtca gcaccatcaa cctccaaaag gcctggggcg ctgccaggag 3900 ggtctccaaa gatgactggc tggaatggct gagacggctg agcctggagc 3950 tgctgaagga ctcatcatcg ccctccctgc gctcctgctg ggccctggca 4000 caggcctaca acccgatggc cagggatctc ttcaatgctg catttgtgtc 4050 ctgctggtct gaactgaatg aagatcaaca ggatgagctc atcagaagca 4100 tcgagttggc cctcacctca caagacatcg ctgaagtcac acagaccctc 4150 ttaaacttgg ctgaattcat ggaacacagt gacaagggcc ccctgccact 4200 gagagatgac aatggcattg ttctgctggg tgagagagct gccaagtgcc 4250 gagcatatgc caaagcacta cactacaaag aactggagtt ccagaaaggc 4300 cccacccctg ccattctaga atctctcatc agcattaata ataagctaca 4350 gcagccggag gcagcggccg gagtgttaga atatgccatg aaacactttg 4400 gagagctgga gatccaggct acctggtatg agaaactgca cgagtgggag 4450 gatgcccttg tggcctatga caagaaaatg gacaccaaca aggacgaccc 4500 agagctgatg ctgggccgca tgcgctgcct cgaggccttg ggggaatggg 4550 gtcaactcca ccagcagtgc tgtgaaaagt ggaccctggt taatgatgag 4600 acccaagcca agatggcccg gatggctgct gcagctgcat ggggtttagg 4650 tcagtgggac agcatggaag aatacacctg tatgatccct cgggacaccc 4700 atgatggggc attttataga gctgtgctgg cactgcatca ggacctcttc 4750 tccttggcac aacagtgcat tgacaaggcc agggacctgc tggatgctga 4800 attaactgcg atggcaggag agagttacag tcgggcatat ggggccatgg 4850 tttcttgcca catgctgtcc gagctggagg aggttatcca gtacaaactt 4900 gtccccgagc gacgagagat catccgccag atctggtggg agagactgca 4950 gggctgccag cgtatcgtag aggactggca gaaaatcctt atggtgcggt 5000 cccttgtggt cagccctcat gaagacatga gaacctggct caagtatgca 5050 agcctgtgcg gcaagagtgg caggctggct cttgctcata aaactttagt 5100 gttgctcctg ggagttgatc cgtctcggca acttgaccat cctctgccaa 5150 cagttcaccc tcaggtgacc tatgcctaca tgaaaaacat gtggaagagt 5200 gcccgcaaga tcgatgcctt ccagcacatg cagcattttg tccagaccat 5250 gcagcaacag gcccagcatg ccatcgctac tgaggaccag cagcataagc 5300 aggaactgca caagctcatg gcccgatgct tcctgaaact tggagagtgg 5350 cagctgaatc tacagggcat caatgagagc acaatcccca aagtgctgca 5400 gtactacagc gccgccacag agcacgaccg cagctggtac aaggcctggc 5450 atgcgtgggc agtgatgaac ttcgaagctg tgctacacta caaacatcag 5500 aaccaagccc gcgatgagaa gaagaaactg cgtcatgcca gcggggccaa 5550 catcaccaac gccaccactg ccgccaccac ggccgccact gccaccacca 5600 ctgccagcac cgagggcagc aacagtgaga gcgaggccga gagcaccgag 5650 aacagcccca ccccatcgcc gctgcagaag aaggtcactg aggatctgtc 5700 caaaaccctc ctgatgtaca cggtgcctgc cgtccagggc ttcttccgtt 5750 ccatctcctt gtcacgaggc aacaacctcc aggatacact cagagttctc 5800 accttatggt ttgattatgg tcactggcca gatgtcaatg aggccttagt 5850 ggagggggtg aaagccatcc agattgatac ctggctacag gttatacctc 5900 agctcattgc aagaattgat acgcccagac ccttggtggg acgtctcatt 5950 caccagcttc tcacagacat tggtcggtac cacccccagg ccctcatcta 6000 cccactgaca gtggcttcta agtctaccac gacagcccgg cacaatgcag 6050 ccaacaagat tctgaagaac atgtgtgagc acagcaacac cctggtccag 6100 caggccatga tggtgagcga ggagctgatc cgagtggcca tcctctggca 6150 tgagatgtgg catgaaggcc tggaagaggc atctcgtttg tactttgggg 6200 aaaggaacgt gaaaggcatg tttgaggtgc tggagccctt gcatgctatg 6250 atggaacggg gcccccagac tctgaaggaa acatccttta atcaggccta 6300 tggtcgagat ttaatggagg cccaagagtg gtgcaggaag tacatgaaat 6350 cagggaatgt caaggacctc acccaagcct gggacctcta ttatcatgtg 6400 ttccgacgaa tctcaaagca gctgcctcag ctcacatcct tagagctgca 6450 atatgtttcc ccaaaacttc tgatgtgccg ggaccttgaa ttggctgtgc 6500 caggaacata tgaccccaac cagccaatca ttcgcattca gtccatagca 6550 ccgtctttgc aagtcatcac atccaagcag aggccccgga aattgacact 6600 tatgggcagc aacggacatg agtttgtttt ccttctaaaa ggccatgaag 6650 atctgcgcca ggatgagcgt gtgatgcagc tcttcggcct ggttaacacc 6700 cttctggcca atgacccaac atctcttcgg aaaaacctca gcatccagag 6750 atacgctgtc atccctttat cgaccaactc gggcctcatt ggctgggttc 6800 cccactgtga cacactgcac gccctcatcc gggactacag ggagaagaag 6850 aagatccttc tcaacatcga gcatcgcatc atgttgcgga tggctccgga 6900 ctatgaccac ttgactctga tgcagaaggt ggaggtgttt gagcatgccg 6950 tcaataatac agctggggac gacctggcca agctgctgtg gctgaaaagc 7000 cccagctccg aggtgtggtt tgaccgaaga accaattata cccgttcttt 7050 agcggtcatg tcaatggttg ggtatatttt aggcctggga gatagacacc 7100 catccaacct gatgctggac cgtctgagtg ggaagatcct gcacattgac 7150 tttggggact gctttgaggt tgctatgacc cgagagaagt ttccagagaa 7200 gattccattt agactaacaa gaatgttgac caatgctatg gaggttacag 7250 gcctggatgg caactacaga atcacatgcc acacagtgat ggaggtgctg 7300 cgagagcaca aggacagtgt catggccgtg ctggaagcct ttgtctatga 7350 ccccttgctg aactggaggc tgatggacac aaataccaaa ggcaacaagc 7400 gatcccgaac gaggacggat tcctactctg ctggccagtc agtcgaaatt 7450 ttggacggtg tggaacttgg agagccagcc cataagaaaa cggggaccac 7500 agtgccagaa tctattcatt ctttcattgg agacggtttg gtgaaaccag 7550 aggccctaaa taagaaagct atccagatta ttaacagggt tcgagataag 7600 ctcactggtc gggacttctc tcatgatgac actttggatg ttccaacgca 7650 agttgagctg ctcatcaaac aagcgacatc ccatgaaaac ctctgccagt 7700 gctatattgg ctggtgccct ttctggtaac tggaggccca gatgtgccca 7750 tcacgttttt tctgaggctt ttgtacttta gtaaatgctt ccactaaact 7800 gaaaccatgg tgagaaagtt tgactttgtt aaatattttg aaatgtaaat 7850 gaaaagaact actgtatatt aaaagttggt ttgaaccaac tttctagctg 7900 ctgttgaaga atatattgtc agaaacacaa ggcttgattt ggttcccagg 7950 acagtgaaac aatagtaata ccacgtaaat caagccattc attttgggga 8000 acagaagatc cataacttta gaaatacggg ttttgactta actcacaaga 8050 gaactcatca taagtacttg ctgatggaag aatgacctag ttgctcctct 8100 caacatgggt acagcaaact cagcacagcc aagaagcctc aggtcgtgga 8150 gaacatggat taggatccta gactgtaaag acacagaaga tgctgacctc 8200 acccctgcca cctatcccaa gacctcactg gtctgtggac agcagcagaa 8250 atgtttgcaa gataggccaa aatgagtaca aaaggtctgt cttccatcag 8300 acccagtgat gctgcgactc acacgcttca attcaagacc tgaccgctag 8350 tagggaggtt tattcagatc gctggcagcc tcggctgagc agatgcacag 8400 aggggatcac tgtgcagtgg gaccaccctc actggccttc tgcagcaggg 8450 ttctgggatg ttttcagtgg tcaaaatact ctgtttagag caagggctca 8500 gaaaacagaa atactgtcat ggaggtgctg aacacaggga aggtctggta 8550 catattggaa attatgagca gaacaaatac tcaactaaat gcacaaagta 8600 taaagtgtag ccatgtctag acaccatgtt gtatcagaat aatttttgtg 8650 ccaataaatg acatcagaat tttaaacata 8680 gatgatcgga tccatggagc cttgttgatc cttaacgagc tggtccgaat 900 cagcagcatg gagggagagc gtctgagaga agaaatggaa gaaatcacac 950 agcagcagct ggtacacgac aagtactgca aagatctcat gggcttcgga 1000 acaaaacctc gtcacattac ccccttcacc agtttccagg ctgtacagcc 1050 ccagcagtca aatgccttgg tggggctgct ggggtacagc tctcaccaag 1100 gcctcatggg atttgggacc tcccccagtc cagctaagtc caccctggtg 1150 gagagccggt gttgcagaga cttgatggag gagaaatttg atcaggtgtg 1200 ctgaaatgca ccagtgggtg ggaatagcaa gaactcgctg atccaaatga 1250 caatccttaa tttgttgccc cgcttggctg cattccgacc ttctgccttc 1300 agtatctcca acagataccc agataccatg aaccatgtcc taagctgtgt 1350 aaggaacgta caagaaggag cagcggcctt ccaagccctg gggctacttt 1400 ctgtggctgt gaggtctgag tttaaggtct atttgcctcg cgtgctggac 1450 atcatccgag cggccctgcc cccaaaggac ttcgcccata agaggcagaa 1500 ggcaatgcag gtggatgcca cagtcttcac ttgcatcagc atgctggctc 1550 gagcaatggg gccaggcatc cagcaggata tcaaggagct gctggagccc 1600 atgctggcag tgggactaag ccctgccctc actgcagtgc tctacgacct 1650 gagccgtcag attccacagc TAAAG aagga cattcaagat gggctactga 1700 aaatgctgtc cctggtcctt atgcacaaac cccttcgcca cccaggcatg 1750 tggcccatca cccaagggcc gctggcctct cctggcctca cgaccctccc 1800 gatgtgggca tgaggccagc gcatcactct tgccctccga acgcttggca 1850 gctttgaatt tgaaggccac tctctgaccc aatttgttcg ccactgtgcg 1900 gatcatttcc tgaacagtga gcacaaggag atccgcatgg aggctgcccg 1950 cgcctgctca cacctgctcc caccctccat ccacctcatc agtggccatg 2000 ctcatgtggt tagccagacc gcagtgcaag tggtggcaga tgtgcttagc 2050 aaactgctcg tagttgggat aacagatcct gaccctgaca ttcgctactg 2100 tgtcttggcg tccctggacg agcgctttga tgcacacctg gcccaggcgg 2150 agaacttgca ggccttgttt gtggctctga atgaccaggt gtttgagatc 2200 cgggagctgg ccatctgcac tgtgggccga ctcagtagca tgaaccctgc 2250 ctttgtcatg cctttcctgc gcaagatgct catccagatt ttgacagagt 2300 tggagcacag tgggattgga agaatcaaag agcagagtgc ccgcatgctg 2350 gggcacctgg tctccaatgc cccccgactc atccgcccct acatggagcc 2400 tattctgaag gcattaattt tgaaactgaa agatccagac cctgatccaa 2450 acccaggtgt gatcaataat gtcctggcaa attggca caataggaga cag 2500 gttagtggcc tggaaatgag gaaatgggtt gatgaacttt ttattatcat 2550 catggacatg ctccaggatt cctctttgtt ggccaaaagg caggtggctc 2600 tgtggaccct gggacagttg gtggccagca ctggctatgt agtagagccc 2650 tacaggaagt accctacttt gcttgaggtg ctactgaatt ttctgaagac 2700 tgagcagaac cagggtacac gcagagaggc catccgtgtg ttagggcttt 2750 taggggcttt ggatccttac aagcacaaag tgaacattgg catgatagac 2800 cagtcccggg atgcctctgc tgtcagcctg agtcaagtca tcagaatcca 2850 gactatagca ggattcctct ctagtgaaat gctggtcaac atgggaaact 2900 tgcctctgga tgagttctac ccagctgtgt ccatggtggc cctgatgcgg 2950 atcttccgag accagtcact ctctcatcat cacaccatgg ttgtccaggc 3000 catcaccttc atcttcaagt ccctgggact caaatgtgtg cagttcctgc 3050 cccaggtcat gcccacgttc cttaacgtca ttcgagtctg tgatggggcc 3100 ttttgttcca atccgggaat atgttggtgt gcagctggga cctttgtgaa 3150 gagccacatc agaccttata tggatgaaat agtcaccctc atgagagaat 3200 gaacacctca tctgggtcat attcagagca cgatcattct tctcattgag 3250 caaattgtgg tagctcttgg gggtgaattt aagctctacc tgccccagct 3300 gatcccacac atg ctgcgtg tcttcatgca tgacaacagc ccaggccgca 3350 ttgtctctat caagttactg gctgcaatcc agctgtttgg cgccaacctg 3400 gatgactacc tgcatttact gctgcctcct attgttaagt tgtttgatgc 3450 ccctgaagct ccactgccat ctcgaaaggc agcgctagag actgtggacc 3500 gcctgacgga gtccctggat ttcactgact atgcctcccg gatcattcac 3550 gaacactgga cctattgttc ccagagccca gaactgcgct ccacagccat 3600 ggacacgctg tcttcacttg tttttcagct ggggaagaag taccaaattt 3650 tcattccaat ggtgaataaa gttctggtgc gacaccgaat caatcatcag 3700 cgctatgatg tgctcatctg cagaattgtc aagggataca cacttgctga 3750 gatcctttga tgaagaggag tttaccagca tcggatgctt aggagtggcc 3800 aaggggatgc attggctagt ggaccagtgg aaacaggacc catgaagaaa 3850 gcaccatcaa ctgcacgtca cctccaaaag gcctggggcg ctgccaggag 3900 ggtctccaaa gatgactggc tggaatggct gagacggctg agcctggagc 3950 tgctgaagga ctcatcatcg ccctccctgc gctcctgctg ggccctggca 4000 caggcctaca acccgatggc cagggatctc ttcaatgctg catttgtgtc 4050 ctgctggtct gaactgaatg aagatcaaca atcagaagca ggatgagctc 4100 cctcacctca tcgagttggc caagacatcg ctgaa gtcac acagaccctc 4150 ttaaacttgg ctgaattcat ggaacacagt gacaagggcc ccctgccact 4200 gagagatgac aatggcattg ttctgctggg tgagagagct gccaagtgcc 4250 gagcatatgc caaagcacta cactacaaag aactggagtt ccagaaaggc 4300 ccattctaga cccacccctg agcattaata atctctcatc ataagctaca 4350 gcagccggag gcagcggccg gagtgttaga atatgccatg aaacactttg 4400 gagagctgga gatccaggct acctggtatg agaaactgca cgagtgggag 4450 tggcctatga gatgcccttg caagaaaatg gacaccaaca aggacgaccc 4500 agagctgatg ctgggccgca tgcgctgcct cgaggccttg ggggaatggg 4550 gtcaactcca ccagcagtgc tgtgaaaagt ggaccctggt taatgatgag 4600 acccaagcca agatggcccg gatggctgct gcagctgcat ggggtttagg 4650 tcagtgggac agcatggaag aatacacctg tatgatccct cgggacaccc 4700 attttataga atgatggggc cactgcatca gctgtgctgg ggacctcttc 4750 tccttggcac aacagtgcat tgacaaggcc agggacctgc tggatgctga 4800 attaactgcg atggcaggag agagttacag tcgggcatat ggggccatgg 4850 tttcttgcca catgctgtcc gagctggagg aggttatcca gtacaaactt 4900 gtccccgagc gacgagagat catccgccag atctggtggg agagactgca 4950 g ggctgccag cgtatcgtag aggactggca gaaaatcctt atggtgcggt 5000 cccttgtggt cagccctcat gaacctggct gaagacatga caagtatgca 5050 agcctgtgcg gcaagagtgg caggctggct cttgctcata aaactttagt 5100 gttgctcctg ggagttgatc cgtctcggca acttgaccat cctctgccaa 5150 cagttcaccc tcaggtgacc tatgcctaca tgaaaaacat gtggaagagt 5200 gcccgcaaga tcgatgcctt ccagcacatg cagcattttg tccagaccat 5250 gcagcaacag gcccagcatg ccatcgctac tgaggaccag cagcataagc 5300 aggaactgca caagctcatg gcccgatgct tcctgaaact tggagagtgg 5350 cagctgaatc tacagggcat caatgagagc aagtgctgca acaatcccca 5400 gtactacagc gccgccacag agcacgaccg cagctggtac aaggcctggc 5450 atgcgtgggc agtgatgaac ttcgaagctg tgctacacta caaacatcag 5500 gcgatgagaa aaccaagccc cgtcatgcca gaagaaactg gcggggccaa 5550 catcaccaac gccaccactg ccgccaccac ggccgccact gccaccacca 5600 ctgccagcac cgagggcagc aacagtgaga gcgaggccga gagcaccgag 5650 aacagcccca ccccatcgcc gctgcagaag aaggtcactg aggatctgtc 5700 ctgatgtaca caaaaccctc cggtgcctgc cgtccagggc ttcttccgtt 5750 ccatctcctt gtcacgaggc aaca acctcc aggatacact cagagttctc 5800 accttatggt ttgattatgg tcactggcca gatgtcaatg aggccttagt 5850 ggagggggtg aaagccatcc agattgatac ctggctacag gttatacctc 5900 agctcattgc aagaattgat acgcccagac ccttggtggg acgtctcatt 5950 caccagcttc tcacagacat tggtcggtac cacccccagg ccctcatcta 6000 gtggcttcta cccactgaca agtctaccac gacagcccgg cacaatgcag 6050 ccaacaagat tctgaagaac atgtgtgagc acagcaacac cctggtccag 6100 tggtgagcga caggccatga cgagtggcca ggagctgatc tcctctggca 6150 tgagatgtgg catgaaggcc tggaagaggc atctcgtttg tactttgggg 6200 aaaggaacgt gaaaggcatg tttgaggtgc tggagccctt gcatgctatg 6250 atggaacggg gcccccagac tctgaaggaa atcaggccta acatccttta 6300 tggtcgagat ttaatggagg cccaagagtg gtgcaggaag tacatgaaat 6350 cagggaatgt caaggacctc acccaagcct gggacctcta ttatcatgtg 6400 tctcaaagca ttccgacgaa gctgcctcag ctcacatcct tagagctgca 6450 atatgtttcc ccaaaacttc tgatgtgccg ggaccttgaa ttggctgtgc 6500 caggaacata tgaccccaac ttcgcattca cagccaatca gtccatagca 6550 ccgtctttgc aagtcatcac atccaagcag aggccccgga aattgac act 6600 tatgggcagc aacggacatg agtttgtttt ccttctaaaa ggccatgaag 6650 atctgcgcca ggatgagcgt gtgatgcagc tcttcggcct ggttaacacc 6700 cttctggcca atgacccaac atctcttcgg aaaaacctca gcatccagag 6750 atacgctgtc atccctttat cgaccaactc gggcctcatt ggctgggttc 6800 cccactgtga cacactgcac gccctcatcc gggactacag ggagaagaag 6850 tcaacatcga aagatccttc atgttgcgga gcatcgcatc tggctccgga 6900 ctatgaccac ttgactctga tgcagaaggt ggaggtgttt gagcatgccg 6950 tcaataatac agctggggac gacctggcca agctgctgtg gctgaaaagc 7000 cccagctccg aggtgtggtt tgaccgaaga accaattata cccgttcttt 7050 agcggtcatg tcaatggttg ggtatatttt aggcctggga gatagacacc 7100 catccaacct gatgctggac cgtctgagtg ggaagatcct gcacattgac 7150 tttggggact gctttgaggt tgctatgacc cgagagaagt ttccagagaa 7200 gattccattt agactaacaa gaatgttgac caatgctatg gaggttacag 7250 gcctggatgg caactacaga atcacatgcc acacagtgat ggaggtgctg 7300 cgagagcaca aggacagtgt catggccgtg ctggaagcct ttgtctatga 7350 ccccttgctg aactggaggc tgatggacac aaataccaaa ggcaacaagc 7400 gatcccgaac gagg acggat tcctactctg ctggccagtc agtcgaaatt 7450 ttggacggtg tggaacttgg agagccagcc cataagaaaa cggggaccac 7500 agtgccagaa tctattcatt ctttcattgg agacggtttg gtgaaaccag 7550 aggccctaaa taagaaagct atccagatta ttaacagggt tcgagataag 7600 ctcactggtc gggacttctc tcatgatgac actttggatg ttccaacgca 7650 agttgagctg ctcatcaaac aagcgacatc ccatgaaaac ctctgccagt 7700 gctatattgg ctggtgccct ttctggtaac gatgtgccca tggaggccca 7750 tcacgttttt tctgaggctt ttgtacttta gtaaatgctt ccactaaact 7800 gaaaccatgg tgagaaagtt tgactttgtt aaatattttg aaatgtaaat 7850 gaaaagaact actgtatatt aaaagttggt ttgaaccaac tttctagctg 7900 ctgttgaaga atatattgtc agaaacacaa ggcttgattt ggttcccagg 7950 aatagtaata acagtgaaac ccacgtaaat caagccattc attttgggga 8000 cataacttta acagaagatc gaaatacggg ttttgactta actcacaaga 8050 gaactcatca taagtacttg ctgatggaag aatgacctag ttgctcctct 8100 caacatgggt acagcaaact cagcacagcc aagaagcctc aggtcgtgga 8150 gaacatggat taggatccta gactgtaaag acacagaaga tgctgacctc 8200 cctatcccaa acccctgcca gacctcactg gtctgt GGAC agcagcagaa 8250 gataggccaa atgtttgcaa aatgagtaca aaaggtctgt cttccatcag 8300 acccagtgat gctgcgactc acacgcttca attcaagacc tgaccgctag 8350 tagggaggtt tattcagatc gctggcagcc tcggctgagc agatgcacag 8400 aggggatcac tgtgcagtgg gaccaccctc actggccttc tgcagcaggg 8450 ttctgggatg ttttcagtgg tcaaaatact ctgtttagag caagggctca 8500 gaaaacagaa atactgtcat ggaggtgctg aacacaggga aggtctggta 8550 attatgagca catattggaa gaacaaatac tcaactaaat gcacaaagta 8600 taaagtgtag ccatgtctag acaccatgtt gtatcagaat aatttttgtg 8650 ccaataaatg acatcagaat tttaaacata 8680

<210> 27 <210> 27

<211> 5830 <211> 5830

<212> ADN <212> DNA

<213> Homo sapiens <213> Homo sapiens

<400> 27 <400> 27

actgagtccc gggaccccgg gagagcggtc agtgtgtggt cgctgcgttt 50 actgagtccc gggaccccgg gagagcggtc agtgtgtggt cgctgcgttt 50

agcctggata tcctctccta ccggcacccg cagacgcccc tgcagccgcc 150 agcctggata tcctctccta ccggcacccg cagacgcccc tgcagccgcc 150

ggtcggcgcc cgggctccct agccctgtgc gctcaactgt cctgcgctgc 200 ggtcggcgcc cgggctccct agccctgtgc gctcaactgt cctgcgctgc 200

ggggtgccgc gagttccacc tccgcgcctc cttctctaga caggcgctgg 250 ggggtgccgc gagttccacc tccgcgcctc cttctctaga caggcgctgg 250

gagaaagaac cggctcccga gttctgggca tttcgcccgg ctcgaggtgc 300 gagaaagaac cggctcccga gttctgggca tttcgcccgg ctcgaggtgc 300

aggatgcaga gcaaggtgct gctggccgtc gccctgtggc tctgcgtgga 350 aggatgcaga gcaaggtgct gctggccgtc gccctgtggc tctgcgtgga 350

gacccgggcc gcctctgtgg gtttgcctag tgtttctctt gatctgccca 400 gacccgggcc gcctctgtgg gtttgcctag tgtttctctt gatctgccca 400

ggctcagcat acaaaaagac atacttacaa ttaaggctaa tacaactctt 450 ggctcagcat acaaaaagac atacttacaa ttaaggctaa tacaactctt 450

caaattactt gcaggggaca gagggacttg gactggcttt ggcccaataa 500 caaattactt gcaggggaca gagggacttg gactggcttt ggcccaataa 500

tcagagtggc agtgagcaaa gggtggaggt gactgagtgc agcgatggcc 550 tcttctgtaa gacactcaca attccaaaag tgatcggaaa tgacactgga 600 gcctacaagt gcttctaccg ggaaactgac ttggcctcgg tcatttatgt 650 ctatgttcaa gattacagat ctccatttat tgcttctgtt agtgaccaac 700 atggagtcgt gtacattact gagaacaaaa acaaaactgt ggtgattcca 750 tgtctcgggt ccatttcaaa tctcaacgtg tcactttgtg caagataccc 800 agaaaagaga tttgttcctg atggtaacag aatttcctgg gacagcaaga 850 agggctttac tattcccagc tacatgatca gctatgctgg catggtcttc 900 tgtgaagcaa aaattaatga tgaaagttac cagtctatta tgtacatagt 950 tgtcgttgta gggtatagga tttatgatgt ggttctgagt ccgtctcatg 1000 gaattgaact atctgttgga gaaaagcttg tcttaaattg tacagcaaga 1050 actgaactaa atgtggggat tgacttcaac tgggaatacc cttcttcgaa 1100 gcatcagcat aagaaacttg taaaccgaga cctaaaaacc cagtctggga 1150 gtgagatgaa gaaatttttg agcaccttaa ctatagatgg tgtaacccgg 1200 agtgaccaag gattgtacac ctgtgcagca tccagtgggc tgatgaccaa 1250 gaagaacagc acatttgtca gggtccatga aaaacctttt gttgcttttg 1300 gaagtggcat ggaatctctg gtggaagcca cggtggggga gcgtgtcaga 1350 atccctgcga agtaccttgg ttacccaccc ccagaaataa aatggtataa 1400 aaatggaata ccccttgagt ccaatcacac aattaaagcg gggcatgtac 1450 tgacgattat ggaagtgagt gaaagagaca caggaaatta cactgtcatc 1500 cttaccaatc ccatttcaaa ggagaagcag agccatgtgg tctctctggt 1550 tgtgtatgtc ccaccccaga ttggtgagaa atctctaatc tctcctgtgg 1600 attcctacca gtacggcacc actcaaacgc tgacatgtac ggtctatgcc 1650 attcctcccc cgcatcacat ccactggtat tggcagttgg aggaagagtg 1700 cgccaacgag cccagccaag ctgtctcagt gacaaaccca tacccttgtg 1750 aagaatggag aagtgtggag gacttccagg gaggaaataa aattgaagtt 1800 aataaaaatc aatttgctct aattgaagga aaaaacaaaa ctgtaagtac 1850 ccttgttatc caagcggcaa atgtgtcagc tttgtacaaa tgtgaagcgg 1900 tcaacaaagt cgggagagga gagagggtga tctccttcca cgtgaccagg 1950 ggtcctgaaa ttactttgca acctgacatg cagcccactg agcaggagag 2000 cgtgtctttg tggtgcactg cagacagatc tacgtttgag aacctcacat 2050 ggtacaagct tggcccacag cctctgccaa tccatgtggg agagttgccc 2100 acacctgttt gcaagaactt ggatactctt tggaaattga atgccaccat 2150 gttctctaat agcacaaatg acattttgat catggagctt aagaatgcat 2200 ccttgcagga ccaaggagac tatgtctgcc ttgctcaaga caggaagacc 2250 aagaaaagac attgcgtggt caggcagctc acagtcctag agcgtgtggc 2300 acccacgatc acaggaaacc tggagaatca gacgacaagt attggggaaa 2350 gcatcgaagt ctcatgcacg gcatctggga atccccctcc acagatcatg 2400 tggtttaaag ataatgagac ccttgtagaa gactcaggca ttgtattgaa 2450 ggatgggaac cggaacctca ctatccgcag agtgaggaag gaggacgaag 2500 gcctctacac ctgccaggca tgcagtgttc ttggctgtgc aaaagtggag 2550 gcatttttca taatagaagg tgcccaggaa aagacgaact tggaaatcat 2600 tattctagta ggcacggcgg tgattgccat gttcttctgg ctacttcttg 2650 tcatcatcct acggaccgtt aagcgggcca atggagggga actgaagaca 2700 ggctacttgt ccatcgtcat ggatccagat gaactcccat tggatgaaca 2750 ttgtgaacga ctgccttatg atgccagcaa atgggaattc cccagagacc 2800 ggctgaagct aggtaagcct cttggccgtg gtgcctttgg ccaagtgatt 2850 gaagcagatg cctttggaat tgacaagaca gcaacttgca ggacagtagc 2900 agtcaaaatg ttgaaagaag gagcaacaca cagtgagcat cgagctctca 2950 tgtctgaact caagatcctc attcatattg gtcaccatct caatgtggtc 3000 aaccttctag gtgcctgtac caagccagga gggccactca tggtgattgt 3050 ggaattctgc aaatttggaa acctgtccac ttacctgagg agcaagagaa 3100 atgaatttgt cccctacaag accaaagggg cacgattccg tcaagggaaa 3150 gactacgttg gagcaatccc tgtggatctg aaacggcgct tggacagcat 3200 caccagtagc cagagctcag ccagctctgg atttgtggag gagaagtccc 3250 tcagtgatgt agaagaagag gaagctcctg aagatctgta taaggacttc 3300 ctgaccttgg agcatctcat ctgttacagc ttccaagtgg ctaagggcat 3350 ggagttcttg gcatcgcgaa agtgtatcca cagggacctg gcggcacgaa 3400 atatcctctt atcggagaag aacgtggtta aaatctgtga ctttggcttg 3450 gcccgggata tttataaaga tccagattat gtcagaaaag gagatgctcg 3500 cctccctttg aaatggatgg ccccagaaac aatttttgac agagtgtaca 3550 caatccagag tgacgtctgg tcttttggtg ttttgctgtg ggaaatattt 3600 tccttaggtg cttctccata tcctggggta aagattgatg aagaattttg 3650 taggcgattg aaagaaggaa ctagaatgag ggcccctgat tatactacac 3700 cagaaatgta ccagaccatg ctggactgct ggcacgggga gcccagtcag 3750 agacccacgt tttcagagtt ggtggaacat ttgggaaatc tcttgcaagc 3800 taatgctcag caggatggca aagactacat tgttcttccg atatcagaga 3850 ctttgagcat ggaagaggat tctggactct ctctgcctac ctcacctgtt 3900 tcctgtatgg aggaggagga agtatgtgac cccaaattcc attatgacaa 3950 cacagcagga atcagtcagt atctgcagaa cagtaagcga aagagccggc 4000 ctgtgagtgt aaaaacattt gaagatatcc cgttagaaga accagaagta 4050 aaagtaatcc cagatgacaa ccagacggac agtggtatgg ttcttgcctc 4100 agaagagctg aaaactttgg aagacagaac caaattatct ccatcttttg 4150 gtggaatggt gcccagcaaa agcagggagt ctgtggcatc tgaaggctca 4200 aaccagacaa gcggctacca gtccggatat cactccgatg acacagacac 4250 caccgtgtac tccagtgagg aagcagaact tttaaagctg atagagattg 4300 gagtgcaaac cggtagcaca gcccagattc tccagcctga ctcggggacc 4350 acactgagct ctcctcctgt ttaaaaggaa gcatccacac cccaactccc 4400 ggacatcaca tgagaggtct gctcagattt tgaagtgttg ttctttccac 4450 cagcaggaag tagccgcatt tgattttcat ttcgacaaca gaaaaaggac 4500 ctcggactgc agggagccag tcttctaggc atatcctgga agaggcttgt 4550 gacccaagaa tgtgtctgtg tcttctccca gtgttgacct gatcctcttt 4600 tttcattcat ttaaaaagca ttatcatgcc cctgctgcgg gtctcaccat 4650 gggtttagaa caaagagctt caagcaatgg ccccatcctc aaagaagtag 4700 cagtacctgg ggagctgaca cttctgtaaa actagaagat aaaccaggca 4750 acgtaagtgt tcgaggtgtt gaagatggga aggatttgca gggctgagtc 4800 tatccaagag gctttgttta ggacgtgggt cccaagccaa gccttaagtg 4850 tggaattcgg attgatagaa aggaagacta acgttacctt gctttggaga 4900 gtactggagc ctgcaaatgc attgtgtttg ctctggtgga ggtgggcatg 4950 gggtctgttc tgaaatgtaa agggttcaga cggggtttct ggttttagaa 5000 ggttgcgtgt tcttcgagtt gggctaaagt agagttcgtt gtgctgtttc 5050 tgactcctaa tgagagttcc ttccagaccg ttagctgtct ccttgccaag 5100 ccccaggaag aaaatgatgc agctctggct ccttgtctcc caggctgatc 5150 ctttattcag aataccacaa agaaaggaca ttcagctcaa ggctccctgc 5200 cgtgttgaag agttctgact gcacaaacca gcttctggtt tcttctggaa 5250 tgaataccct catatctgtc ctgatgtgat atgtctgaga ctgaatgcgg 5300 gaggttcaat gtgaagctgt gtgtggtgtc aaagtttcag gaaggatttt 5350 acccttttgt tcttccccct gtccccaacc cactctcacc ccgcaaccca 5400 tcagtatttt agttatttgg cctctactcc agtaaacctg attgggtttg 5450 ttcactctct gaatgattat tagccagact tcaaaattat tttatagccc 5500 aaattataac atctattgta ttatttagac ttttaacata tagagctatt 5550 tctactgatt tttgcccttg ttctgtcctt tttttcaaaa aagaaaatgt 5600 gttttttgtt tggtaccata gtgtgaaatg ctgggaacaa tgactataag 5650 acatgctatg gcacatatat ttatagtctg tttatgtaga aacaaatgta 5700 atatattaaa gccttatata taatgaactt tgtactattc acattttgta 5750 tcagtattat gtagcataac aaaggtcata atgctttcag caattgatgt 5800 cattttatta aagaacattg aaaaacttga 5830 tcagagtggc agtgagcaaa gggtggaggt gactgagtgc agcgatggcc 550 gacactcaca tcttctgtaa attccaaaag tgatcggaaa tgacactgga to 600 gcctacaagt gcttctaccg ggaaactgac ttggcctcgg tcatttatgt 650 ctatgttcaa gattacagat ctccatttat tgcttctgtt agtgaccaac 700 atggagtcgt gtacattact gagaacaaaa acaaaactgt ggtgattcca to 750 tgtctcgggt ccatttcaaa tctcaacgtg tcactttgtg caagataccc 800 agaaaagaga tttgttcctg atggtaacag aatttcctgg gacagcaaga 850 agggctttac tattcccagc tacatgatca gctatgctgg catggtcttc 900 aaattaatga tgtgaagcaa tgaaagttac cagtctatta tgtacatagt 950 gggtatagga tgtcgttgta tttatgatgt ggttctgagt ccgtctcatg 1000 gaattgaact atctgttgga gaaaagcttg tcttaaattg tacagcaaga 1050 actgaactaa atgtggggat tgacttcaac tgggaatacc cttcttcgaa 1100 gcatcagcat aagaaacttg taaaccgaga cctaaaaacc cagtctggga 1150 gtgagatgaa gaaatttttg agcaccttaa ctatagatgg tgtaacccgg 1200 agtgaccaag gattgtacac ctgtgcagca tccagtgggc tgatgaccaa 1250 acatttgtca gaagaacagc gggtccatga aaaacctttt gttgcttttg 1300 gaagtggcat ggaatctctg gtggaagcca cggtggggga gcgtgtcaga 1350 atccctgcga agtaccttgg ttacccaccc ccagaaataa aatggtataa 1400 aaatggaata ccccttgagt ccaatcacac aattaaagcg gggcatgtac 1450 tgacgattat ggaagtgagt gaaagagaca caggaaatta cactgtcatc 1500 cttaccaatc ccatttcaaa ggagaagcag agccatgtgg tctctctggt 1550 ccaccccaga tgtgtatgtc ttggtgagaa atctctaatc tctcctgtgg 1600 attcctacca gtacggcacc actcaaacgc tgacatgtac ggtctatgcc 1650 attcctcccc cgcatcacat ccactggtat tggcagttgg aggaagagtg 1700 cgccaacgag cccagccaag ctgtctcagt gacaaaccca tacccttgtg 1750 aagaatggag aagtgtggag gacttccagg gaggaaataa aattgaagtt 1800 aatttgctct aataaaaatc aaaaacaaaa aattgaagga ctgtaagtac 1850 caagcggcaa ccttgttatc atgtgtcagc tttgtacaaa tgtgaagcgg 1900 cgggagagga tcaacaaagt gagagggtga tctccttcca cgtgaccagg 1950 ttactttgca ggtcctgaaa acctgacatg cagcccactg agcaggagag 2000 cgtgtctttg tggtgcactg cagacagatc tacgtttgag aacctcacat 2050 ggtacaagct tggcccacag cctctgccaa tccatgtggg agagttgccc 2100 acacctgttt gcaagaactt ggatactctt tggaaattga atgccaccat 21 50 gttctctaat agcacaaatg acattttgat catggagctt aagaatgcat 2200 ccttgcagga ccaaggagac tatgtctgcc ttgctcaaga caggaagacc 2250 aagaaaagac attgcgtggt caggcagctc acagtcctag agcgtgtggc 2300 acccacgatc acaggaaacc tggagaatca gacgacaagt attggggaaa 2350 gcatcgaagt ctcatgcacg gcatctggga atccccctcc acagatcatg 2400 tggtttaaag ataatgagac ccttgtagaa gactcaggca ttgtattgaa 2450 cggaacctca ggatgggaac ctatccgcag agtgaggaag gaggacgaag 2500 ctgccaggca gcctctacac tgcagtgttc ttggctgtgc aaaagtggag 2550 gcatttttca taatagaagg tgcccaggaa aagacgaact tggaaatcat 2600 tattctagta ggcacggcgg tgattgccat gttcttctgg ctacttcttg 2650 tcatcatcct acggaccgtt aagcgggcca actgaagaca atggagggga 2700 ggctacttgt ccatcgtcat ggatccagat gaactcccat tggatgaaca 2750 ttgtgaacga ctgccttatg atgccagcaa atgggaattc cccagagacc 2800 ggctgaagct aggtaagcct cttggccgtg gtgcctttgg ccaagtgatt 2850 gaagcagatg cctttggaat tgacaagaca gcaacttgca ggacagtagc 2900 agtcaaaatg ttgaaagaag gagcaacaca cgagctctca cagtgagcat 2950 tgtctgaact caagatcct c attcatattg gtcaccatct caatgtggtc 3000 aaccttctag gtgcctgtac gggccactca caagccagga tggtgattgt 3050 ggaattctgc aaatttggaa acctgtccac ttacctgagg agcaagagaa 3100 atgaatttgt cccctacaag accaaagggg cacgattccg tcaagggaaa 3150 gactacgttg gagcaatccc tgtggatctg aaacggcgct tggacagcat 3200 caccagtagc cagagctcag ccagctctgg atttgtggag gagaagtccc 3250 tcagtgatgt agaagaagag gaagctcctg aagatctgta taaggacttc 3300 ctgaccttgg agcatctcat ctgttacagc ttccaagtgg ctaagggcat 3350 gcatcgcgaa ggagttcttg agtgtatcca cagggacctg gcggcacgaa 3400 atatcctctt atcggagaag aacgtggtta aaatctgtga ctttggcttg 3450 tttataaaga gcccgggata tccagattat gtcagaaaag gagatgctcg 3500 cctccctttg aaatggatgg ccccagaaac aatttttgac agagtgtaca 3550 caatccagag tgacgtctgg tcttttggtg ttttgctgtg ggaaatattt 3600 tccttaggtg cttctccata tcctggggta aagattgatg aagaattttg 3650 taggcgattg aaagaaggaa ctagaatgag ggcccctgat tatactacac 3700 cagaaatgta ccagaccatg ctggactgct ggcacgggga gcccagtcag 3750 agacccacgt tttcagagtt ggtggaacat ttgggaaatc tcttgcaagc 3800 taatgctcag caggatggca aagactacat tgttcttccg atatcagaga 3850 ctttgagcat ggaagaggat tctggactct ctctgcctac ctcacctgtt 3900 tcctgtatgg aggaggagga agtatgtgac cccaaattcc attatgacaa 3950 atcagtcagt cacagcagga atctgcagaa cagtaagcga aagagccggc 4000 ctgtgagtgt aaaaacattt gaagatatcc cgttagaaga accagaagta 4050 aaagtaatcc cagatgacaa ccagacggac agtggtatgg ttcttgcctc 4100 agaagagctg aaaactttgg aagacagaac caaattatct ccatcttttg 4150 gtggaatggt gcccagcaaa agcagggagt ctgtggcatc tgaaggctca 4200 aaccagacaa gcggctacca gtccggatat cactccgatg acacagacac 4250 caccgtgtac tccagtgagg aagcagaact tttaaagctg atagagattg 4300 cggtagcaca gagtgcaaac tccagcctga gcccagattc ctcggggacc 4350 acactgagct ctcctcctgt ttaaaaggaa gcatccacac cccaactccc 4400 ggacatcaca tgagaggtct gctcagattt tgaagtgttg ttctttccac 4450 cagcaggaag tagccgcatt tgattttcat ttcgacaaca gaaaaaggac 4500 ctcggactgc agggagccag tcttctaggc atatcctgga agaggcttgt 4550 gacccaagaa tgtgtctgtg tcttctccca gtgttgacct gatcctcttt 4600 tttcattc at ttaaaaagca ttatcatgcc cctgctgcgg gtctcaccat 4650 gggtttagaa caaagagctt caagcaatgg ccccatcctc aaagaagtag 4700 ggagctgaca cagtacctgg actagaagat cttctgtaaa aaaccaggca 4750 tcgaggtgtt acgtaagtgt gaagatggga aggatttgca gggctgagtc 4800 tatccaagag gctttgttta ggacgtgggt cccaagccaa gccttaagtg 4850 attgatagaa tggaattcgg acgttacctt aggaagacta gctttggaga 4900 gtactggagc ctgcaaatgc attgtgtttg ctctggtgga ggtgggcatg 4950 tgaaatgtaa gggtctgttc agggttcaga cggggtttct ggttttagaa 5000 ggttgcgtgt tcttcgagtt gggctaaagt agagttcgtt gtgctgtttc 5050 tgactcctaa tgagagttcc ttccagaccg ttagctgtct ccttgccaag 5100 ccccaggaag aaaatgatgc agctctggct ccttgtctcc caggctgatc 5150 aataccacaa ctttattcag ttcagctcaa agaaaggaca ggctccctgc 5200 cgtgttgaag agttctgact gcacaaacca gcttctggtt tcttctggaa 5250 tgaataccct catatctgtc ctgatgtgat atgtctgaga ctgaatgcgg 5300 gaggttcaat gtgaagctgt gtgtggtgtc aaagtttcag gaaggatttt 5350 acccttttgt tcttccccct gtccccaacc cactctcacc ccgcaaccca 5400 tcagtatttt agttatttgg cctctactcc agtaaacctg attgggtttg 5450 ttcactctct gaatgattat tagccagact tcaaaattat tttatagccc 5500 aaattataac atctattgta ttatttagac ttttaacata tagagctatt 5550 tctactgatt tttgcccttg ttctgtcctt tttttcaaaa aagaaaatgt 5600 gttttttgtt tggtaccata gtgtgaaatg ctgggaacaa tgactataag 5650 acatgctatg gcacatatat ttatagtctg tttatgtaga aacaaatgta 5700 gccttatata atatattaaa taatgaactt tgtactattc acattttgta 5750 tcagtattat gtagcataac aaaggtcata atgctttcag caattgatgt 5800 5830 aagaacattg cattttatta aaaaacttga

<210> 28 <210> 28

<211> 1759 <211> 1759

<212> ADN <212> DNA

<213> Homo sapiens <213> Homo sapiens

<400> 28 <400> 28

cccctgcctc tcggactcgg gctgcggcgt cagccttctt cgggcctcgg 50 cccctgcctc tcggactcgg gctgcggcgt cagccttctt cgggcctcgg 50

cagcggtagc ggctcgctcg cctcagcccc agcgcccctc ggctaccctc 100 cagcggtagc ggctcgctcg cctcagcccc agcgcccctc ggctaccctc 100

ggcccaggcc cgcagcgccg cccgccctcg gccgccccga cgccggcctg 150 ggcccaggcc cgcagcgccg cccgccctcg gccgccccga cgccggcctg 150

ggccgcggcc gcagccccgg gctcgcgtag gcgccgaccg ctcccggccc 200 ggccgcggcc gcagccccgg gctcgcgtag gcgccgaccg ctcccggccc 200

gccccctatg ggccccggct agaggcgccg ccgccgccgg cccgcggagc 250 gccccctatg ggccccggct agaggcgccg ccgccgccgg cccgcggagc 250

cccgatgctg gcccggagga agccggtgct gccggcgctc accatcaacc 300 cccgatgctg gcccggagga agccggtgct gccggcgctc accatcaacc 300

ctaccatcgc cgagggccca tcccctacca gcgagggcgc ctccgaggca 350 ctaccatcgc cgagggccca tcccctacca gcgagggcgc ctccgaggca 350

aacctggtgg acctgcagaa gaagctggag gagctggaac ttgacgagca 400 aacctggtgg acctgcagaa gaagctggag gagctggaac ttgacgagca 400

gcagaagaag cggctggaag cctttctcac ccagaaagcc aaggtcggcg 450 gcagaagaag cggctggaag cctttctcac ccagaaagcc aaggtcggcg 450

aactcaaaga cgatgacttc gaaaggatct cagagctggg cgcgggcaac 500 aactcaaaga cgatgacttc gaaaggatct cagagctggg cgcgggcaac 500

ggcggggtgg tcaccaaagt ccagcacaga ccctcgggcc tcatcatggc 550 ggcggggtgg tcaccaaagt ccagcacaga ccctcgggcc tcatcatggc 550

caggaagctg atccaccttg agatcaagcc ggccatccgg aaccagatca 600 caggaagctg atccaccttg agatcaagcc ggccatccgg aaccagatca 600

tccgcgagct gcaggtcctg cacgaatgca actcgccgta catcgtgggc 650 tccgcgagct gcaggtcctg cacgaatgca actcgccgta catcgtgggc 650

ttctacgggg ccttctacag tgacggggag atcagcattt gcatggaaca 700 ttctacgggg ccttctacag tgacggggag atcagcattt gcatggaaca 700

catggacggc ggctccctgg accaggtgct gaaagaggcc aagaggattc 750 catggacggc ggctccctgg accaggtgct gaaagaggcc aagaggattc 750

ccgaggagat cctggggaaa gtcagcatcg cggttctccg gggcttggcg 800 ccgaggagat cctggggaaa gtcagcatcg cggttctccg gggcttggcg 800

tacctccgag agaagcacca gatcatgcac cgagatgtga agccctccaa 850 tacctccgag agaagcacca gatcatgcac cgagatgtga agccctccaa 850

catcctcgtg aactctagag gggagatcaa gctgtgtgac ttcggggtga 900 catcctcgtg aactctagag gggagatcaa gctgtgtgac ttcggggtga 900

gcggccagct catagactcc atggccaact ccttcgtggg cacgcgctcc 950 gcggccagct catagactcc atggccaact ccttcgtggg cacgcgctcc 950

tacatggctc cggagcggtt gcagggcaca cattactcgg tgcagtcgga 1000 tacatggctc cggagcggtt gcagggcaca cattactcgg tgcagtcgga 1000

catctggagc atgggcctgt ccctggtgga gctggccgtc ggaaggtacc 1050 catctggagc atgggcctgt ccctggtgga gctggccgtc ggaaggtacc 1050

ccatcccccc gcccgacgcc aaagagctgg aggccatctt tggccggccc 1100 ccatcccccc gcccgacgcc aaagagctgg aggccatctt tggccggccc 1100

gtggtcgacg gggaagaagg agagcctcac agcatctcgc ctcggccgag 1150 gtggtcgacg gggaagaagg agagcctcac agcatctcgc ctcggccgag 1150

gccccccggg cgccccgtca gcggtcacgg gatggatagc cggcctgcca 1200 gccccccggg cgccccgtca gcggtcacgg gatggatagc cggcctgcca 1200

tggccatctt tgaactcctg gactatattg tgaacgagcc acctcctaag 1250 tggccatctt tgaactcctg gactatattg tgaacgagcc acctcctaag 1250

ctgcccaacg gtgtgttcac ccccgacttc caggagtttg tcaataaatg 1300 ctgcccaacg gtgtgttcac ccccgacttc caggagtttg tcaataaatg 1300

cctcatcaag aacccagcgg agcgggcgga cctgaagatg ctcacaaacc 1350 acaccttcat caagcggtcc gaggtggaag aagtggattt tgccggctgg 1400 ttgtgtaaaa ccctgcggct gaaccagccc ggcacaccca cgcgcaccgc 1450 cgtgtgacag tggccgggct ccctgcgtcc cgctggtgac ctgcccaccg 1500 tccctgtcca tgccccgccc ttccagctga ggacaggctg gcgcctccac 1550 ccaccctcct gcctcacccc tgcggagagc accgtggcgg ggcgacagcg 1600 catgcaggaa cgggggtctc ctctcctgcc cgtcctggcc ggggtgcctc 1650 tggggacggg cgacgctgct gtgtgtggtc tcagaggctc tgcttcctta 1700 ggttacaaaa caaaacaggg agagaaaaag caaaaaaaaa aaaaaaaaaa 1750 aaaaaaaaa 1759 cctcatcaag aacccagcgg agcgggcgga cctgaagatg ctcacaaacc 1350 acaccttcat caagcggtcc gaggtggaag aagtggattt tgccggctgg 1400 ttgtgtaaaa ccctgcggct gaaccagccc ggcacaccca cgcgcaccgc 1450 cgtgtgacag tggccgggct ccctgcgtcc cgctggtgac ctgcccaccg 1500 tccctgtcca tgccccgccc ttccagctga ggacaggctg gcgcctccac 1550 ccaccctcct gcctcacccc tgcggagagc accgtggcgg ggcgacagcg 1600 catgcaggaa cgggggtctc ctctcctgcc cgtcctggcc ggggtgcctc 1650 tggggacggg cgacgctgct gtgtgtggtc tcagaggctc tgcttcctta 1700 ggttacaaaa caaaacaggg agagaaaaag caaaaaaaaa aaaaaaaaaa 1750 aaaaaaaaa 1759

<210> 29 <210> 29

<211> 6641 <211> 6641

<212> ADN <212> DNA

<213> Homo sapiens <213> Homo sapiens

<400> 29 <400> 29

ccaatttatc aggaggtgtt tggaaagata acatcaacat ggctctagtt 550 ccaatttatc aggaggtgtt tggaaagata acatcaacat ggctctagtt 550

gtcgacacct actatgatga tcaactcatt agctgtggca gcgtcaacag 600 gtcgacacct actatgatga tcaactcatt agctgtggca gcgtcaacag 600

agggacctgc cagcgacatg tctttcccca caatcatact gctgacatac 650 agggacctgc cagcgacatg tctttcccca caatcatact gctgacatac 650

agtcggaggt tcactgcata ttctccccac agatagaaga gcccagccag 700 agtcggaggt tcactgcata ttctccccac agatagaaga gcccagccag 700

tgtcctgact gtgtggtgag cgccctggga gccaaagtcc tttcatctgt 750 tgtcctgact gtgtggtgag cgccctggga gccaaagtcc tttcatctgt 750

aaaggaccgg ttcatcaact tctttgtagg caataccata aattcttctt 800 aaaggaccgg ttcatcaact tctttgtagg caataccata aattcttctt 800

atttcccaga tcatccattg cattcgatat cagtgagaag gctaaaggaa 850 atttcccaga tcatccattg cattcgatat cagtgagaag gctaaaggaa 850

acgaaagatg gttttatgtt tttgacggac cagtcctaca ttgatgtttt 900 acgaaagatg gttttatgtt tttgacggac cagtcctaca ttgatgtttt 900

acctgagttc agagattctt accccattaa gtatgtccat gcctttgaaa 950 acctgagttc agagattctt accccattaa gtatgtccat gcctttgaaa 950

gcaacaattt tatttacttc ttgacggtcc aaagggaaac tctagatgct 1000 gcaacaattt tatttacttc ttgacggtcc aaagggaaac tctagatgct 1000

cagacttttc acacaagaat aatcaggttc tgttccataa actctggatt 1050 cagacttttc acacaagaat aatcaggttc tgttccataa actctggatt 1050

gcattcctac atggaaatgc ctctggagtg tattctcaca gaaaagagaa 1100 aaaagagatc cacaaagaag gaagtgttta atatacttca ggctgcgtat 1150 gtcagcaagc ctggggccca gcttgctaga caaataggag ccagcctgaa 1200 tgatgacatt cttttcgggg tgttcgcaca aagcaagcca gattctgccg 1250 aaccaatgga tcgatctgcc atgtgtgcat tccctatcaa atatgtcaac 1300 gacttcttca acaagatcgt caacaaaaac aatgtgagat gtctccagca 1350 tttttacgga cccaatcatg agcactgctt taataggaca cttctgagaa 1400 attcatcagg ctgtgaagcg cgccgtgatg aatatcgaac agagtttacc 1450 acagctttgc agcgcgttga cttattcatg ggtcaattca gcgaagtcct 1500 cttaacatct atatccacct tcattaaagg agacctcacc atagctaatc 1550 ttgggacatc agagggtcgc ttcatgcagg ttgtggtttc tcgatcagga 1600 ccatcaaccc ctcatgtgaa ttttctcctg gactcccatc cagtgtctcc 1650 agaagtgatt gtggagcata cattaaacca aaatggctac acactggtta 1700 tcactgggaa gaagatcacg aagatcccat tgaatggctt gggctgcaga 1750 catttccagt cctgcagtca atgcctctct gccccaccct ttgttcagtg 1800 tggctggtgc cacgacaaat gtgtgcgatc ggaggaatgc ctgagcggga 1850 catggactca acagatctgt ctgcctgcaa tctacaaggt tttcccaaat 1900 agtgcacccc ttgaaggagg gacaaggctg accatatgtg gctgggactt 1950 tggatttcgg aggaataata aatttgattt aaagaaaact agagttctcc 2000 ttggaaatga gagctgcacc ttgactttaa gtgagagcac gatgaataca 2050 ttgaaatgca cagttggtcc tgccatgaat aagcatttca atatgtccat 2100 aattatttca aatggccacg ggacaacaca atacagtaca ttctcctatg 2150 tggatcctgt aataacaagt atttcgccga aatacggtcc tatggctggt 2200 ggcactttac ttactttaac tggaaattac ctaaacagtg ggaattctag 2250 acacatttca attggtggaa aaacatgtac tttaaaaagt gtgtcaaaca 2300 gtattcttga atgttatacc ccagcccaaa ccatttcaac tgagtttgct 2350 gttaaattga aaattgactt agccaaccga gagacaagca tcttcagtta 2400 ccgtgaagat cccattgtct atgaaattca tccaaccaaa tcttttatta 2450 gtggtgggag cacaataaca ggtgttggga aaaacctgaa ttcagttagt 2500 gtcccgagaa tggtcataaa tgtgcatgaa gcaggaagga actttacagt 2550 ggcatgtcaa catcgctcta attcagagat aatctgttgt accactcctt 2600 ccctgcaaca gctgaatctg caactccccc tgaaaaccaa agcctttttc 2650 atgttagatg ggatcctttc caaatacttt gatctcattt atgtacataa 2700 tcctgtgttt aagccttttg aaaagccagt gatgatctca atgggcaatg 2750 aaaatgtact ggaaattaag ggaaatgata ttgaccctga agcagttaaa 2800 ggtgaagtgt taaaagttgg aaataagagc tgtgagaata tacacttaca 2850 ttctgaagcc gttttatgca cggtccccaa tgacctgctg aaattgaaca 2900 gcgagctaaa tatagagtgg aagcaagcaa tttcttcaac cgtccttgga 2950 aaagtaatag ttcaaccaga tcagaatttc acaggattga ttgctggtgt 3000 tgtctcaata tcaacagcac tgttattact acttgggttt ttcctgtggc 3050 tgaaaaagag aaagcaaatt aaagatctgg gcagtgaatt agttcgctac 3100 gatgcaagag tacacactcc tcatttggat aggcttgtaa gtgcccgaag 3150 tgtaagccca actacagaaa tggtttcaaa tgaatctgta gactaccgag 3200 ctacttttcc agaagatcag tttcctaatt catctcagaa cggttcatgc 3250 cgacaagtgc agtatcctct gacagacatg tcccccatcc taactagtgg 3300 ggactctgat atatccagtc cattactgca aaatactgtc cacattgacc 3350 tcagtgctct aaatccagag ctggtccagg cagtgcagca tgtagtgatt 3400 gggcccagta gcctgattgt gcatttcaat gaagtcatag gaagagggca 3450 ttttggttgt gtatatcatg ggactttgtt ggacaatgat ggcaagaaaa 3500 ttcactgtgc tgtgaaatcc ttgaacagaa tcactgacat aggagaagtt 3550 tcccaatttc tgaccgaggg aatcatcatg aaagatttta gtcatcccaa 3600 tgtcctctcg ctcctgggaa tctgcctgcg aagtgaaggg tctccgctgg 3650 tggtcctacc atacatgaaa catggagatc ttcgaaattt cattcgaaat 3700 gagactcata atccaactgt aaaagatctt attggctttg gtcttcaagt 3750 agccaaaggc atgaaatatc ttgcaagcaa aaagtttgtc cacagagact 3800 tggctgcaag aaactgtatg ctggatgaaa aattcacagt caaggttgct 3850 gattttggtc ttgccagaga catgtatgat aaagaatact atagtgtaca 3900 caacaaaaca ggtgcaaagc tgccagtgaa gtggatggct ttggaaagtc 3950 tgcaaactca aaagtttacc accaagtcag atgtgtggtc ctttggcgtg 4000 ctcctctggg agctgatgac aagaggagcc ccaccttatc ctgacgtaaa 4050 cacctttgat ataactgttt acttgttgca agggagaaga ctcctacaac 4100 ccgaatactg cccagacccc ttatatgaag taatgctaaa atgctggcac 4150 cctaaagccg aaatgcgccc atccttttct gaactggtgt cccggatatc 4200 agcgatcttc tctactttca ttggggagca ctatgtccat gtgaacgcta 4250 cttatgtgaa cgtaaaatgt gtcgctccgt atccttctct gttgtcatca 4300 gaagataacg ctgatgatga ggtggacaca cgaccagcct ccttctggga 4350 gacatcatag tgctagtact atgtcaaagc aacagtccac actttgtcca 4400 atggtttttt cactgcctga cctttaaaag gccatcgata ttctttgctc 4450 ttgccaaaat tgcactatta taggacttgt attgttattt aaattactgg 4500 attctaagga atttcttatc tgacagagca tcagaaccag aggcttggtc 4550 ccacaggcca cggaccaatg gcctgcagcc gtgacaacac tcctgtcata 4600 ttggagtcca aaacttgaat tctgggttga attttttaaa aatcaggtac 4650 cacttgattt catatgggaa attgaagcag gaaatattga gggcttcttg 4700 atcacagaaa actcagaaga gatagtaatg ctcaggacag gagcggcagc 4750 cccagaacag gccactcatt tagaattcta gtgtttcaaa acacttttgt 4800 gtgttgtatg gtcaataaca tttttcatta ctgatggtgt cattcaccca 4850 ttaggtaaac attccctttt aaatgtttgt ttgttttttg agacaggatc 4900 tcactctgtt gccagggctg tagtgcagtg gtgtgatcat agctcactgc 4950 aacctccacc tcccaggctc aagcctcccg aatagctggg actacaggcg 5000 cacaccacca tccccggcta atttttgtat tttttgtaga gacggggttt 5050 tgccatgttg ccaaggctgg tttcaaactc ctggactcaa gaaatccacc 5100 cacctcagcc tcccaaagtg ctaggattac aggcatgagc cactgcgccc 5150 agcccttata aatttttgta tagacattcc tttggttgga agaatattta 5200 taggcaatac agtcaaagtt tcaaaatagc atcacacaaa acatgtttat 5250 aaatgaacag gatgtaatgt acatagatga cattaagaaa atttgtatga 5300 aataatttag tcatcatgaa atatttagtt gtcatataaa aacccactgt 5350 ttgagaatga tgctactctg atctaatgaa tgtgaacatg tagatgtttt 5400 gtgtgtattt ttttaaatga aaactcaaaa taagacaagt aatttgttga 5450 taaatatttt taaagataac tcagcatgtt tgtaaagcag gatacatttt 5500 actaaaaggt tcattggttc caatcacagc tcataggtag agcaaagaaa 5550 gggtggatgg attgaaaaga ttagcctctg tctcggtggc aggttcccac 5600 ctcgcaagca attggaaaca aaacttttgg ggagttttat tttgcattag 5650 ggtgtgtttt atgttaagca aaacatactt tagaaacaaa tgaaaaaggc 5700 aattgaaaat cccagctatt tcacctagat ggaatagcca ccctgagcag 5750 aactttgtga tgcttcattc tgtggaattt tgtgcttgct actgtatagt 5800 gcatgtggtg taggttactc taactggttt tgtcgacgta aacatttaaa 5850 gtgttatatt ttttataaaa atgtttattt ttaatgatat gagaaaaatt 5900 ttgttaggcc acaaaaacac tgcactgtga acattttaga aaaggtatgt 5950 cagactggga ttaatgacag catgattttc aatgactgta aattgcgata 6000 aggaaatgta ctgattgcca atacacccca ccctcattac atcatcagga 6050 cttgaagcca agggttaacc cagcaagcta caaagagggt gtgtcacact 6100 gaaactcaat agttgagttt ggctgttgtt gcaggaaaat gattataact 6150 aaaagctctc tgatagtgca gagacttacc agaagacaca aggaattgta 6200 ctgaagagct attacaatcc aaatattgcc gtttcataaa tgtaataagt 6250 aatactaatt cacagagtat tgtaaatggt ggatgacaaa agaaaatctg 6300 ctctgtggaa agaaagaact gtctctacca gggtcaagag catgaacgca 6350 tcaatagaaa gaactcgggg aaacatccca tcaacaggac tacacacttg 6400 tatatacatt cttgagaaca ctgcaatgtg aaaatcacgt ttgctattta 6450 taaacttgtc cttagattaa tgtgtctgga cagattgtgg gagtaagtga 6500 ttcttctaag aattagatac ttgtcactgc ctatacctgc agctgaactg 6550 aatggtactt cgtatgttaa tagttgttct gataaatcat gcaattaaag 6600 taaagtgatg caacatcttg taaaaaaaaa aaaaaaaaaa a 6641 gcattcctac atggaaatgc ctctggagtg tattctcaca gaaaagagaa 1100 aaaagagatc cacaaagaag gaagtgttta atatacttca ggctgcgtat 1150 ctggggccca gtcagcaagc gcttgctaga caaataggag ccagcctgaa 1200 tgatgacatt cttttcgggg tgttcgcaca aagcaagcca gattctgccg 1250 aaccaatgga tcgatctgcc atgtgtgcat tccctatcaa atatgtcaac 1300 gacttcttca acaagatcgt caacaaaaac aatgtgagat gtctccagca 1350 tttttacgga cccaatcatg agcactgctt taataggaca cttctgagaa 1400 attcatcagg ctgtgaagcg cgccgtgatg aatatcgaac agagtttacc 1450 agcgcgttga acagctttgc cttattcatg ggtcaattca gcgaagtcct 1500 cttaacatct atatccacct tcattaaagg agacctcacc atagctaatc 1550 ttgggacatc agagggtcgc ttcatgcagg ttgtggtttc tcgatcagga 1600 ccatcaaccc ctcatgtgaa ttttctcctg gactcccatc cagtgtctcc 1650 gtggagcata agaagtgatt cattaaacca aaatggctac acactggtta 1700 tcactgggaa gaagatcacg aagatcccat tgaatggctt gggctgcaga 1750 cctgcagtca catttccagt atgcctctct gccccaccct ttgttcagtg 1800 tggctggtgc cacgacaaat gtgtgcgatc ggaggaatgc ctgagcggga ctg 1850 catggactca acagatctgt cctgcaa tctacaaggt tttcccaaat 1900 agtgcacccc ttgaaggagg gacaaggctg accatatgtg gctgggactt 1950 tggatttcgg aggaataata aatttgattt aaagaaaact agagttctcc 2000 ttggaaatga gagctgcacc ttgactttaa gtgagagcac gatgaataca 2050 ttgaaatgca cagttggtcc tgccatgaat aagcatttca atatgtccat 2100 aatggccacg aattatttca ggacaacaca atacagtaca ttctcctatg 2150 tggatcctgt aataacaagt atttcgccga aatacggtcc tatggctggt 2200 ggcactttac ttactttaac tggaaattac ctaaacagtg ggaattctag 2250 attggtggaa acacatttca aaacatgtac tttaaaaagt gtgtcaaaca 2300 gtattcttga atgttatacc ccagcccaaa ccatttcaac tgagtttgct 2350 aaattgactt gttaaattga gagacaagca agccaaccga tcttcagtta 2400 ccgtgaagat cccattgtct atgaaattca tcttttatta tccaaccaaa 2450 cacaataaca gtggtgggag ggtgttggga aaaacctgaa ttcagttagt 2500 tggtcataaa gtcccgagaa tgtgcatgaa gcaggaagga actttacagt 2550 catcgctcta ggcatgtcaa attcagagat aatctgttgt accactcctt 2600 ccctgcaaca gctgaatctg caactccccc tgaaaaccaa agcctttttc 2650 atgttagatg ggatcctttc caaatacttt gatctcattt atgta Cataa 2700 tcctgtgttt aagccttttg aaaagccagt gatgatctca atgggcaatg 2750 aaaatgtact ggaaattaag ttgaccctga ggaaatgata agcagttaaa 2800 ggtgaagtgt taaaagttgg aaataagagc tacacttaca tgtgagaata 2850 gttttatgca ttctgaagcc cggtccccaa tgacctgctg aaattgaaca 2900 gcgagctaaa tatagagtgg aagcaagcaa tttcttcaac cgtccttgga 2950 aaagtaatag ttcaaccaga tcagaatttc acaggattga ttgctggtgt 3000 tgtctcaata tcaacagcac tgttattact acttgggttt ttcctgtggc 3050 tgaaaaagag aaagcaaatt aaagatctgg gcagtgaatt agttcgctac 3100 gatgcaagag tacacactcc tcatttggat aggcttgtaa gtgcccgaag 3150 actacagaaa tgtaagccca tgaatctgta tggtttcaaa gactaccgag 3200 ctacttttcc agaagatcag tttcctaatt catctcagaa cggttcatgc 3250 cgacaagtgc agtatcctct gacagacatg tcccccatcc taactagtgg 3300 ggactctgat atatccagtc cattactgca aaatactgtc cacattgacc 3350 tcagtgctct aaatccagag ctggtccagg cagtgcagca tgtagtgatt 3400 gggcccagta gcctgattgt gcatttcaat gaagtcatag gaagagggca 3450 ttttggttgt gtatatcatg ggactttgtt ggacaatgat ggcaagaaaa 3500 ttcactgtgc t gtgaaatcc ttgaacagaa tcactgacat aggagaagtt 3550 tcccaatttc tgaccgaggg aatcatcatg aaagatttta gtcatcccaa 3600 tgtcctctcg ctcctgggaa tctgcctgcg aagtgaaggg tctccgctgg 3650 tggtcctacc atacatgaaa catggagatc ttcgaaattt cattcgaaat 3700 gagactcata atccaactgt aaaagatctt attggctttg gtcttcaagt 3750 agccaaaggc atgaaatatc ttgcaagcaa aaagtttgtc cacagagact 3800 tggctgcaag aaactgtatg ctggatgaaa aattcacagt caaggttgct 3850 ttgccagaga gattttggtc catgtatgat aaagaatact atagtgtaca 3900 ggtgcaaagc caacaaaaca tgccagtgaa gtggatggct ttggaaagtc 3950 tgcaaactca aaagtttacc accaagtcag atgtgtggtc ctttggcgtg 4000 ctcctctggg agctgatgac aagaggagcc ccaccttatc ctgacgtaaa 4050 ataactgttt cacctttgat acttgttgca agggagaaga ctcctacaac 4100 ccgaatactg cccagacccc ttatatgaag taatgctaaa atgctggcac 4150 cctaaagccg aaatgcgccc atccttttct gaactggtgt cccggatatc 4200 tctactttca agcgatcttc ttggggagca ctatgtccat gtgaacgcta 4250 cttatgtgaa cgtaaaatgt gtcgctccgt atccttctct gttgtcatca 4300 gaagataacg ggtggacaca ctgatgatga cga ccagcct ccttctggga 4350 gacatcatag tgctagtact atgtcaaagc aacagtccac actttgtcca 4400 atggtttttt cactgcctga cctttaaaag gccatcgata ttctttgctc 4450 ttgccaaaat tgcactatta taggacttgt attgttattt aaattactgg 4500 attctaagga atttcttatc tgacagagca tcagaaccag aggcttggtc 4550 ccacaggcca cggaccaatg gcctgcagcc gtgacaacac tcctgtcata 4600 aaacttgaat ttggagtcca attttttaaa tctgggttga aatcaggtac 4650 cacttgattt catatgggaa attgaagcag gaaatattga gggcttcttg 4700 actcagaaga atcacagaaa gatagtaatg ctcaggacag gagcggcagc 4750 cccagaacag gccactcatt tagaattcta gtgtttcaaa acacttttgt 4800 gtcaataaca gtgttgtatg ctgatggtgt tttttcatta cattcaccca 4850 ttaggtaaac attccctttt aaatgtttgt ttgttttttg agacaggatc tcactctgtt 4900 gccagggctg tagtgcagtg gtgtgatcat agctcactgc aacctccacc 4950 tcccaggctc aagcctcccg aatagctggg actacaggcg 5000 tccccggcta cacaccacca atttttgtat tttttgtaga gacggggttt 5050 tgccatgttg ccaaggctgg tttcaaactc ctggactcaa gaaatccacc 5100 cacctcagcc tcccaaagtg ctaggattac aggcatgagc cactgcgccc 5150 agcccttata tagacattcc aatttttgta tttggttgga agaatattta 5200 taggcaatac agtcaaagtt tcaaaatagc atcacacaaa acatgtttat 5250 gatgtaatgt aaatgaacag acatagatga cattaagaaa atttgtatga 5300 aataatttag tcatcatgaa atatttagtt gtcatataaa aacccactgt 5350 ttgagaatga tgctactctg atctaatgaa tgtgaacatg tagatgtttt 5400 ttttaaatga gtgtgtattt aaactcaaaa taagacaagt aatttgttga 5450 taaatatttt taaagataac tcagcatgtt tgtaaagcag gatacatttt 5500 actaaaaggt tcattggttc caatcacagc tcataggtag agcaaagaaa 5550 attgaaaaga gggtggatgg ttagcctctg tctcggtggc aggttcccac 5600 attggaaaca ctcgcaagca aaacttttgg ggagttttat tttgcattag 5650 atgttaagca ggtgtgtttt aaacatactt tagaaacaaa tgaaaaaggc 5700 aattgaaaat cccagctatt tcacctagat ggaatagcca ccctgagcag 5750 aactttgtga tgcttcattc tgtggaattt tgtgcttgct actgtatagt 5800 gcatgtggtg taggttactc taactggttt tgtcgacgta aacatttaaa 5850 gtgttatatt ttttataaaa atgtttattt ttaatgatat gagaaaaatt 5900 ttgttaggcc acaaaaacac tgcactgtga acattttaga aaaggtatgt 5950 cagactggga ttaatgacag ca tgattttc aatgactgta aattgcgata 6000 ctgattgcca aggaaatgta atacacccca ccctcattac atcatcagga 6050 cttgaagcca agggttaacc cagcaagcta caaagagggt gtgtcacact 6100 gaaactcaat agttgagttt ggctgttgtt gcaggaaaat gattataact 6150 tgatagtgca aaaagctctc agaagacaca gagacttacc aggaattgta 6200 ctgaagagct attacaatcc aaatattgcc gtttcataaa tgtaataagt 6250 aatactaatt cacagagtat tgtaaatggt ggatgacaaa agaaaatctg 6300 agaaagaact ctctgtggaa gtctctacca gggtcaagag catgaacgca 6350 tcaatagaaa gaactcgggg aaacatccca tcaacaggac tacacacttg 6400 tatatacatt cttgagaaca ctgcaatgtg aaaatcacgt ttgctattta 6450 cttagattaa taaacttgtc tgtgtctgga cagattgtgg gagtaagtga 6500 ttcttctaag aattagatac ttgtcactgc ctatacctgc agctgaactg 6550 aatggtactt cgtatgttaa tagttgttct gataaatcat gcaattaaag 6600 taaagtgatg caacatcttg taaaaaaaaa aaaaaaaaaa to 6641

<210> 30 <210> 30

<211> 3724 <211> 3724

<212> ADN <212> DNA

<213> Homo sapiens <213> Homo sapiens

<400> 30 <400> 30

tctccctcgg cgccgccgcc gccgcccgcg gggctgggac ccgatgcggt 50 tctccctcgg cgccgccgcc gccgcccgcg gggctgggac ccgatgcggt 50

tagagccgcg gagcctggaa gagccccgag cgtttctgct ttgggacaac 100 tagagccgcg gagcctggaa gagccccgag cgtttctgct ttgggacaac 100

catacatcta attccttaaa gtagttttat atgtaaaact tgcaaagaat 150 catacatcta attccttaaa gtagttttat atgtaaaact tgcaaagaat 150

cagaacaatg cctccacgac catcatcagg tgaactgtgg ggcatccact 200 cagaacaatg cctccacgac catcatcagg tgaactgtgg ggcatccact 200

tgatgccccc aagaatccta gtagaatgtt tactaccaaa tggaatgata 250 tgatgccccc aagaatccta gtagaatgtt tactaccaaa tggaatgata 250

gtgactttag aatgcctccg tgaggctaca ttaataacca taaagcatga 300 gtgactttag aatgcctccg tgaggctaca ttaataacca taaagcatga 300

actatttaaa gaagcaagaa aataccccct ccatcaactt cttcaagatg 350 actatttaaa gaagcaagaa aataccccct ccatcaactt cttcaagatg 350

aatcttctta cattttcgta agtgttactc aagaagcaga aagggaagaa 400 aatcttctta cattttcgta agtgttactc aagaagcaga aagggaagaa 400

ttttttgatg aaacaagacg actttgtgac cttcggcttt ttcaaccctt 450 ttttttgatg aaacaagacg actttgtgac cttcggcttt ttcaaccctt 450

tttaaaagta attgaaccag taggcaaccg tgaagaaaag atcctcaatc 500 tttaaaagta attgaaccag taggcaaccg tgaagaaaag atcctcaatc 500

gagaaattgg ttttgctatc ggcatgccag tgtgtgaatt tgatatggtt 550 gagaaattgg ttttgctatc ggcatgccag tgtgtgaatt tgatatggtt 550

aaagatccag aagtacagga cttccgaaga aatattctga acgtttgtaa 600 aaagatccag aagtacagga cttccgaaga aatattctga acgtttgtaa 600

agaagctgtg gatcttaggg acctcaattc acctcatagt agagcaatgt 650 agaagctgtg gatcttaggg acctcaattc acctcatagt agagcaatgt 650

atgtctatcc tccaaatgta gaatcttcac cagaattgcc aaagcacata 700 atgtctatcc tccaaatgta gaatcttcac cagaattgcc aaagcacata 700

tataataaat tagataaagg gcaaataata gtggtgatct gggtaatagt 750 tataataaat tagataaagg gcaaataata gtggtgatct gggtaatagt 750

ttctccaaat aatgacaagc agaagtatac tctgaaaatc aaccatgact 800 ttctccaaat aatgacaagc agaagtatac tctgaaaatc aaccatgact 800

gtgtaccaga acaagtaatt gctgaagcaa tcaggaaaaa aactcgaagt 850 gtgtaccaga acaagtaatt gctgaagcaa tcaggaaaaa aactcgaagt 850

atgttgctat cctctgaaca actaaaactc tgtgttttag aatatcaggg 900 atgttgctat cctctgaaca actaaaactc tgtgttttag aatatcaggg 900

caagtatatt ttaaaagtgt gtggatgtga tgaatacttc ctagaaaaat 950 caagtatatt ttaaaagtgt gtggatgtga tgaatacttc ctagaaaaat 950

atcctctgag tcagtataag tatataagaa gctgtataat gcttgggagg 1000 atcctctgag tcagtataag tatataagaa gctgtataat gcttgggagg 1000

atgcccaatt tgatgttgat ggctaaagaa agcctttatt ctcaactgcc 1050 atgcccaatt tgatgttgat ggctaaagaa agcctttatt ctcaactgcc 1050

aatggactgt tttacaatgc catcttattc cagacgcatt tccacagcta 1100 caccatatat gaatggagaa acatctacaa aatccctttg ggttataaat 1150 agtgcactca gaataaaaat tctttgtgca acctacgtga atgtaaatat 1200 tcgagacatt gataagatct atgttcgaac aggtatctac catggaggag 1250 aacccttatg tgacaatgtg aacactcaaa gagtaccttg ttccaatccc 1300 aggtggaatg aatggctgaa ttatgatata tacattcctg atcttcctcg 1350 tgctgctcga ctttgccttt ccatttgctc tgttaaaggc cgaaagggtg 1400 ctaaagagga acactgtcca ttggcatggg gaaatataaa cttgtttgat 1450 tacacagaca ctctagtatc tggaaaaatg gctttgaatc tttggccagt 1500 acctcatgga ttagaagatt tgctgaaccc tattggtgtt actggatcaa 1550 atccaaataa agaaactcca tgcttagagt tggagtttga ctggttcagc 1600 agtgtggtaa agttcccaga tatgtcagtg attgaagagc atgccaattg 1650 gtctgtatcc cgagaagcag gatttagcta ttcccacgca ggactgagta 1700 acagactagc tagagacaat gaattaaggg aaaatgacaa agaacagctc 1750 aaagcaattt ctacacgaga tcctctctct gaaatcactg agcaggagaa 1800 agattttcta tggagtcaca gacactattg tgtaactatc cccgaaattc 1850 tacccaaatt gcttctgtct gttaaatgga attctagaga tgaagtagcc 1900 cagatgtatt gcttggtaaa agattggcct ccaatcaaac ctgaacaggc 1950 tatggaactt ctggactgta attacccaga tcctatggtt cgaggttttg 2000 ctgttcggtg cttggaaaaa tatttaacag atgacaaact ttctcagtat 2050 ttaattcagc tagtacaggt cctaaaatat gaacaatatt tggataactt 2100 gcttgtgaga tttttactga agaaagcatt gactaatcaa aggattgggc 2150 actttttctt ttggcattta aaatctgaga tgcacaataa aacagttagc 2200 cagaggtttg gcctgctttt ggagtcctat tgtcgtgcat gtgggatgta 2250 tttgaagcac ctgaataggc aagtcgaggc aatggaaaag ctcattaact 2300 taactgacat tctcaaacag gagaagaagg atgaaacaca aaaggtacag 2350 atgaagtttt tagttgagca aatgaggcga ccagatttca tggatgctct 2400 acagggcttt ctgtctcctc taaaccctgc tcatcaacta ggaaacctca 2450 ggcttgaaga gtgtcgaatt atgtcctctg caaaaaggcc actgtggttg 2500 aattgggaga acccagacat catgtcagag ttactgtttc agaacaatga 2550 gatcatcttt aaaaatgggg atgatttacg gcaagatatg ctaacacttc 2600 aaattattcg tattatggaa aatatctggc aaaatcaagg tcttgatctt 2650 cgaatgttac cttatggttg tctgtcaatc ggtgactgtg tgggacttat 2700 tgaggtggtg cgaaattctc acactattat gcaaattcag tgcaaaggcg 2750 gcttgaaagg tgcactgcag ttcaacagcc acacactaca tcagtggctc 2800 aaagacaaga acaaaggaga aatatatgat gcagccattg acctgtttac 2850 acgttcatgt gctggatact gtgtagctac cttcattttg ggaattggag 2900 atcgtcacaa tagtaacatc atggtgaaag acgatggaca actgtttcat 2950 atagattttg gacacttttt ggatcacaag aagaaaaaat ttggttataa 3000 acgagaacgt gtgccatttg ttttgacaca ggatttctta atagtgatta 3050 gtaaaggagc ccaagaatgc acaaagacaa gagaatttga gaggtttcag 3100 gagatgtgtt acaaggctta tctagctatt cgacagcatg ccaatctctt 3150 cataaatctt ttctcaatga tgcttggctc tggaatgcca gaactacaat 3200 cttttgatga cattgcatac attcgaaaga ccctagcctt agataaaact 3250 gagcaagagg ctttggagta tttcatgaaa caaatgaatg atgcacatca 3300 tggtggctgg acaacaaaaa tggattggat cttccacaca attaaacagc 3350 atgcattgaa ctgaaaagat aactgagaaa atgaaagctc actctggatt 3400 ccacactgca ctgttaataa ctctcagcag gcaaagaccg attgcatagg 3450 aattgcacaa tccatgaaca gcattagaat ttacagcaag aacagaaata 3500 aaatactata taatttaaat aatgtaaacg caaacagggt ttgatagcac 3550 ttaaactagt tcatttcaaa attaagcttt agaataatgc gcaatttcat 3600 gttatgcctt aagtccaaaa aggtaaactt tgaagattgt ttgtatcttt 3650 ttttaaaaaa caaaacaaaa caaaaatccc caaaatatat agaaatgatg 3700 gagaaggaaa aaaaaaaaaa aaaa 3724 aatggactgt tttacaatgc catcttattc cagacgcatt tccacagcta 1100 gaatggagaa caccatatat acatctacaa aatccctttg ggttataaat 1150 agtgcactca gaataaaaat tctttgtgca acctacgtga atgtaaatat 1200 tcgagacatt gataagatct atgttcgaac aggtatctac catggaggag 1250 aacccttatg tgacaatgtg aacactcaaa gagtaccttg ttccaatccc 1300 aggtggaatg aatggctgaa ttatgatata tacattcctg atcttcctcg 1350 tgctgctcga ctttgccttt ccatttgctc tgttaaaggc cgaaagggtg 1400 acactgtcca ctaaagagga ttggcatggg gaaatataaa cttgtttgat 1450 tacacagaca ctctagtatc tggaaaaatg gctttgaatc tttggccagt 1500 acctcatgga ttagaagatt tgctgaaccc tattggtgtt actggatcaa 1550 agaaactcca atccaaataa tgcttagagt tggagtttga ctggttcagc 1600 agttcccaga agtgtggtaa tatgtcagtg attgaagagc atgccaattg 1650 gtctgtatcc cgagaagcag gatttagcta ttcccacgca ggactgagta 1700 acagactagc tagagacaat gaattaaggg aaaatgacaa agaacagctc 1750 aaagcaattt ctacacgaga tcctctctct gaaatcactg agcaggagaa 1800 tggagtcaca agattttcta gacactattg tgtaactatc cccgaaattc 1850 tacccaaatt gt gcttctgtct taaatgga attctagaga tgaagtagcc 1900 cagatgtatt gcttggtaaa agattggcct ccaatcaaac ctgaacaggc 1950 ctggactgta tatggaactt attacccaga tcctatggtt cgaggttttg 2000 ctgttcggtg cttggaaaaa tatttaacag atgacaaact ttctcagtat 2050 ttaattcagc tagtacaggt cctaaaatat gaacaatatt tggataactt 2100 tttttactga gcttgtgaga agaaagcatt gactaatcaa aggattgggc 2150 actttttctt ttggcattta aaatctgaga tgcacaataa aacagttagc 2200 cagaggtttg gcctgctttt ggagtcctat tgtcgtgcat gtgggatgta 2250 tttgaagcac ctgaataggc aagtcgaggc aatggaaaag ctcattaact 2300 taactgacat tctcaaacag gagaagaagg atgaaacaca aaaggtacag 2350 tagttgagca atgaagtttt aatgaggcga ccagatttca tggatgctct 2400 acagggcttt ctgtctcctc taaaccctgc ggaaacctca tcatcaacta 2450 ggcttgaaga gtgtcgaatt atgtcctctg caaaaaggcc actgtggttg 2500 aattgggaga acccagacat catgtcagag ttactgtttc agaacaatga 2550 gatcatcttt aaaaatgggg atgatttacg gcaagatatg ctaacacttc 2600 aaattattcg tattatggaa aatatctggc aaaatcaagg tcttgatctt 2650 cgaatgttac cttatggttg tctgtcaatc ggtgactgtg TGGG acttat 2700 tgaggtggtg cgaaattctc acactattat gcaaattcag tgcaaaggcg 2750 gcttgaaagg tgcactgcag ttcaacagcc acacactaca tcagtggctc 2800 acaaaggaga aaagacaaga aatatatgat gcagccattg acctgtttac 2850 acgttcatgt gctggatact gtgtagctac cttcattttg ggaattggag 2900 atcgtcacaa tagtaacatc atggtgaaag acgatggaca actgtttcat 2950 atagattttg gacacttttt ggatcacaag aagaaaaaat ttggttataa 3000 acgagaacgt gtgccatttg ttttgacaca atagtgatta ggatttctta 3050 gtaaaggagc ccaagaatgc acaaagacaa gagaatttga gaggtttcag 3100 gagatgtgtt acaaggctta tctagctatt cgacagcatg ccaatctctt 3150 cataaatctt ttctcaatga tgcttggctc tggaatgcca gaactacaat 3200 cttttgatga cattgcatac attcgaaaga ccctagcctt agataaaact 3250 gagcaagagg tttcatgaaa ctttggagta atgcacatca caaatgaatg 3300 tggtggctgg acaacaaaaa tggattggat cttccacaca attaaacagc 3350 atgcattgaa ctgaaaagat aactgagaaa atgaaagctc actctggatt 3400 ctgttaataa ccacactgca ctctcagcag gcaaagaccg attgcatagg 3450 tccatgaaca aattgcacaa gcattagaat ttacagcaag aacagaaata 3500 aaatactata taatttaaat aatgtaaacg caaacagggt ttgatagcac 3550 ttaaactagt tcatttcaaa attaagcttt agaataatgc gcaatttcat 3600 gttatgcctt aagtccaaaa aggtaaactt tgaagattgt ttgtatcttt 3650 caaaacaaaa ttttaaaaaa caaaaatccc caaaatatat agaaatgatg 3700 gagaaggaaa aaaaaaaaaa yyyy 3724

<210> 31 <210> 31

<211> 2204 <211> 2204

<212> ADN <212> DNA

<213> Homo sapiens <213> Homo sapiens

<400> 31 <400> 31

gagcggtgcg gaggctctgc tcggatcgag gtctgcagcg cagcttcggg 50 gagcggtgcg gaggctctgc tcggatcgag gtctgcagcg cagcttcggg 50

agcatgagtg ctgcagtgac tgcagggaag ctggcacggg caccggccga 100 agcatgagtg ctgcagtgac tgcagggaag ctggcacggg caccggccga 100

ccctgggaaa gccggggtcc ccggagttgc agctcccgga gctccggcgg 150 ccctgggaaa gccggggtcc ccggagttgc agctcccgga gctccggcgg 150

cggctccacc ggcgaaagag atcccggagg tcctagtgga cccacgcagc 200 cggctccacc ggcgaaagag atcccggagg tcctagtgga cccacgcagc 200

cggcggcgct atgtgcgggg ccgctttttg ggcaagggcg gctttgccaa 250 cggcggcgct atgtgcgggg ccgctttttg ggcaagggcg gctttgccaa 250

gtgcttcgag atctcggacg cggacaccaa ggaggtgttc gcgggcaaga 300 gtgcttcgag atctcggacg cggacaccaa ggaggtgttc gcgggcaaga 300

ttgtgcctaa gtctctgctg ctcaagccgc accagaggga gaagatgtcc 350 ttgtgcctaa gtctctgctg ctcaagccgc accagaggga gaagatgtcc 350

atggaaatat ccattcaccg cagcctcgcc caccagcacg tcgtaggatt 400 atggaaatat ccattcaccg cagcctcgcc caccagcacg tcgtaggatt 400

ccacggcttt ttcgaggaca acgacttcgt gttcgtggtg ttggagctct 450 ccacggcttt ttcgaggaca acgacttcgt gttcgtggtg ttggagctct 450

gccgccggag gtctctcctg gagctgcaca agaggaggaa agccctgact 500 gccgccggag gtctctcctg gagctgcaca agaggaggaa agccctgact 500

gagcctgagg cccgatacta cctacggcaa attgtgcttg gctgccagta 550 gagcctgagg cccgatacta cctacggcaa attgtgcttg gctgccagta 550

cctgcaccga aaccgagtta ttcatcgaga cctcaagctg ggcaaccttt 600 tcctgaatga agatctggag gtgaaaatag gggattttgg actggcaacc 650 aaagtcgaat atgacgggga gaggaagaag accctgtgtg ggactcctaa 700 ttacatagct cccgaggtgc tgagcaagaa agggcacagt ttcgaggtgg 750 atgtgtggtc cattgggtgt atcatgtata ccttgttagt gggcaaacca 800 ccttttgaga cttcttgcct aaaagagacc tacctccgga tcaagaagaa 850 tgaatacagt attcccaagc acatcaaccc cgtggccgcc tccctcatcc 900 agaagatgct tcagacagat cccactgccc gcccaaccat taacgagctg 950 cttaatgacg agttctttac ttctggctat atccctgccc gtctccccat 1000 cacctgcctg accattccac caaggttttc gattgctccc agcagcctgg 1050 accccagcaa ccggaagccc ctcacagtcc tcaataaagg cttggagaac 1100 cccctgcctg agcgtccccg ggaaaaagaa gaaccagtgg ttcgagagac 1150 aggtgaggtg gtcgactgcc acctcagtga catgctgcag cagctgcaca 1200 gtgtcaatgc ctccaagccc tcggagcgtg ggctggtcag gcaagaggag 1250 gctgaggatc ctgcctgcat ccccatcttc tgggtcagca agtgggtgga 1300 ctattcggac aagtacggcc ttgggtatca gctctgtgat aacagcgtgg 1350 gggtgctctt caatgactca acacgcctca tcctctacaa tgatggtgac 1400 agcctgcagt acatagagcg tgacggcact gagtcctacc tcaccgtgag 1450 ttcccatccc aactccttga tgaagaagat caccctcctt aaatatttcc 1500 gcaattacat gagcgagcac ttgctgaagg caggtgccaa catcacgccg 1550 cgcgaaggtg atgagctcgc ccggctgccc tacctacgga cctggttccg 1600 cacccgcagc gccatcatcc tgcacctcag caacggcagc gtgcagatca 1650 acttcttcca ggatcacacc aagctcatct tgtgcccact gatggcagcc 1700 gtgacctaca tcgacgagaa gcgggacttc cgcacatacc gcctgagtct 1750 cctggaggag tacggctgct gcaaggagct ggccagccgg ctccgctacg 1800 cccgcactat ggtggacaag ctgctgagct cacgctcggc cagcaaccgt 1850 ctcaaggcct cctaatagct gccctcccct ccggactggt gccctcctca 1900 ctcccacctg catctggggc ccatactggt tggctcccgc ggtgccatgt 1950 ctgcagtgtg ccccccagcc ccggtggctg ggcagagctg catcatcctt 2000 gcaggtgggg gttgctgtgt aagttatttt tgtacatgtt cgggtgtggg 2050 ttctacagcc ttgtccccct ccccctcaac cccaccatat gaattgtaca 2100 gaatatttct attgaattcg gaactgtcct ttccttggct ttatgcacat 2150 taaacagatg tgaatattca aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 2200 aaaa 2204 cctgcaccga aaccgagtta ttcatcgaga cctcaagctg ggcaaccttt 600 tcctgaatga agatctggag gtgaaaatag gggattttgg actggcaacc 650 aaagtcgaat atgacgggga gaggaagaag accctgtgtg ggactcctaa 700 ttacatagct cccgaggtgc tgagcaagaa agggcacagt ttcgaggtgg 750 atgtgtggtc cattgggtgt atcatgtata ccttgttagt gggcaaacca 800 ccttttgaga cttcttgcct aaaagagacc tacctccgga tcaagaagaa 850 tgaatacagt attcccaagc acatcaaccc cgtggccgcc tccctcatcc 900 agaagatgct tcagacagat cccactgccc gcccaaccat taacgagctg 950 cttaatgacg agttctttac ttctggctat atccctgccc gtctccccat 1000 cacctgcctg accattccac caaggttttc gattgctccc agcagcctgg 1050 accccagcaa ccggaagccc ctcacagtcc tcaataaagg cttggagaac 1100 cccctgcctg agcgtccccg ggaaaaagaa gaaccagtgg ttcgagagac 1150 aggtgaggtg gtcgactgcc acctcagtga catgctgcag cagctgcaca 1200 gtgtcaatgc ctccaagccc tcggagcgtg ggctggtcag gcaagaggag 1250 gctgaggatc ctgcctgcat ccccatcttc tgggtcagca agtgggtgga 1300 ctattcggac aagtacggcc ttgggtatca gctctgtgat aacagcgtgg 1350 caatgactca gggtgctctt acacgcctca tcctctacaa tgatggtgac 1400 agcctgcagt acatagagcg tgacggcact gagtcctacc tcaccgtgag 1450 ttcccatccc aactccttga tgaagaagat caccctcctt aaatatttcc 1500 gcaattacat gagcgagcac ttgctgaagg caggtgccaa catcacgccg 1550 cgcgaaggtg atgagctcgc ccggctgccc tacctacgga cctggttccg 1600 cacccgcagc gccatcatcc tgcacctcag caacggcagc gtgcagatca 1650 acttcttcca ggatcacacc aagctcatct tgtgcccact gatggcagcc 1700 tcgacgagaa gtgacctaca gcgggacttc cgcacatacc gcctgagtct 1750 cctggaggag tacggctgct gcaaggagct ggccagccgg ctccgctacg 1800 cccgcactat ggtggacaag ctgctgagct cacgctcggc cagcaaccgt 1850 ctcaaggcct cctaatagct gccctcccct ccggactggt gccctcctca 1900 ctcccacctg catctggggc ccatactggt tggctcccgc ggtgccatgt 1950 ctgcagtgtg ccccccagcc ccggtggctg ggcagagctg catcatcctt 2000 gcaggtgggg gttgctgtgt aagttatttt tgtacatgtt cgggtgtggg 2050 ttctacagcc ttgtccccct ccccctcaac cccaccatat gaattgtaca 2100 gaatatttct attgaattcg gaactgtcct ttccttggct ttatgcacat taaacagatg 2150 tgaatattca aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 2 200 aaaa 2204

<210> 32 <211> 6825 <210> 32 <211> 6825

<212> ADN <212> DNA

<213> Homo sapiens <213> Homo sapiens

<400> 32 <400> 32

gcgcccgccg tgtgagcagc agcagcggct ggtctgtcaa ccggagcccg 50 gcgcccgccg tgtgagcagc agcagcggct ggtctgtcaa ccggagcccg 50

agcccgagca gcctgcggcc agcagcgtcc tcgcaagccg agcgcccagg 100 agcccgagca gcctgcggcc agcagcgtcc tcgcaagccg agcgcccagg 100

cgcgccagga gcccgcagca gcggcagcag cgcgccgggc cgcccgggaa 150 cgcgccagga gcccgcagca gcggcagcag cgcgccgggc cgcccgggaa 150

gcctccgtcc ccgcggcggc ggcggcggcg gcggcaacat ggcctcggct 200 gcctccgtcc ccgcggcggc ggcggcggcg gcggcaacat ggcctcggct 200

ggtaacgccg ccgagcccca ggaccgcggc ggcggcggca gcggctgtat 250 ggtaacgccg ccgagcccca ggaccgcggc ggcggcggca gcggctgtat 250

cggtgccccg ggacggccgg ctggaggcgg gaggcgcaga cggacggggg 300 cggtgccccg ggacggccgg ctggaggcgg gaggcgcaga cggacggggg 300

ggctgcgccg tgctgccgcg ccggaccggg actatctgca ccggcccagc 350 ggctgcgccg tgctgccgcg ccggaccggg actatctgca ccggcccagc 350

tactgcgacg ccgccttcgc tctggagcag atttccaagg ggaaggctac 400 tactgcgacg ccgccttcgc tctggagcag atttccaagg ggaaggctac 400

tggccggaaa gcgccgctgt ggctgagagc gaagtttcag agactcttat 450 tggccggaaa gcgccgctgt ggctgagagc gaagtttcag agactcttat 450

ttaaactggg ttgttacatt caaaaaaact gcggcaagtt cttggttgtg 500 ttaaactggg ttgttacatt caaaaaaact gcggcaagtt cttggttgtg 500

ggcctcctca tatttggggc cttcgcggtg ggattaaaag cagcgaacct 550 ggcctcctca tatttggggc cttcgcggtg ggattaaaag cagcgaacct 550

cgagaccaac gtggaggagc tgtgggtgga agttggagga cgagtaagtc 600 cgagaccaac gtggaggagc tgtgggtgga agttggagga cgagtaagtc 600

gtgaattaaa ttatactcgc cagaagattg gagaagaggc tatgtttaat 650 gtgaattaaa ttatactcgc cagaagattg gagaagaggc tatgtttaat 650

cctcaactca tgatacagac ccctaaagaa gaaggtgcta atgtcctgac 700 cctcaactca tgatacagac ccctaaagaa gaaggtgcta atgtcctgac 700

cacagaagcg ctcctacaac acctggactc ggcactccag gccagccgtg 750 cacagaagcg ctcctacaac acctggactc ggcactccag gccagccgtg 750

tccatgtata catgtacaac aggcagtgga aattggaaca tttgtgttac 800 tccatgtata catgtacaac aggcagtgga aattggaaca tttgtgttac 800

aaatcaggag agcttatcac agaaacaggt tacatggatc agataataga 850 aaatcaggag agcttatcac agaaacaggt tacatggatc agataataga 850

atatctttac ccttgtttga ttattacacc tttggactgc ttctgggaag 900 atatctttac ccttgtttga ttattacacc tttggactgc ttctgggaag 900

gggcgaaatt acagtctggg acagcatacc tcctaggtaa acctcctttg 950 gggcgaaatt acagtctggg acagcatacc tcctaggtaa acctcctttg 950

cggtggacaa acttcgaccc tttggaattc ctggaagagt taaagaaaat 1000 cggtggacaa acttcgaccc tttggaattc ctggaagagt taaagaaaat 1000

aaactatcaa gtggacagct gggaggaaat gctgaataag gctgaggttg 1050 aaactatcaa gtggacagct gggaggaaat gctgaataag gctgaggttg 1050

gtcatggtta catggaccgc ccctgcctca atccggccga tccagactgc 1100 gtcatggtta catggaccgc ccctgcctca atccggccga tccagactgc 1100

cccgccacag cccccaacaa aaattcaacc aaacctcttg atatggccct 1150 cccgccacag cccccaacaa aaattcaacc aaacctcttg atatggccct 1150

tgttttgaat ggtggatgtc atggcttatc cagaaagtat atgcactggc 1200 tgttttgaat ggtggatgtc atggcttatc cagaaagtat atgcactggc 1200

aggaggagtt gattgtgggt ggcacagtca agaacagcac tggaaaactc 1250 aggaggagtt gattgtgggt ggcacagtca agaacagcac tggaaaactc 1250

gtcagcgccc atgccctgca gaccatgttc cagttaatga ctcccaagca 1300 gtcagcgccc atgccctgca gaccatgttc cagttaatga ctcccaagca 1300

aatgtacgag cacttcaagg ggtacgagta tgtctcacac atcaactgga 1350 aatgtacgag cacttcaagg ggtacgagta tgtctcacac atcaactgga 1350

acgaggacaa agcggcagcc atcctggagg cctggcagag gacatatgtg 1400 acgaggacaa agcggcagcc atcctggagg cctggcagag gacatatgtg 1400

gaggtggttc atcagagtgt cgcacagaac tccactcaaa aggtgctttc 1450 gaggtggttc atcagagtgt cgcacagaac tccactcaaa aggtgctttc 1450

cttcaccacc acgaccctgg acgacatcct gaaatccttc tctgacgtca 1500 cttcaccacc acgaccctgg acgacatcct gaaatccttc tctgacgtca 1500

gtgtcatccg cgtggccagc ggctacttac tcatgctcgc ctatgcctgt 1550 gtgtcatccg cgtggccagc ggctacttac tcatgctcgc ctatgcctgt 1550

ctaaccatgc tgcgctggga ctgctccaag tcccagggtg ccgtggggct 1600 ctaaccatgc tgcgctggga ctgctccaag tcccagggtg ccgtggggct 1600

ggctggcgtc ctgctggttg cactgtcagt ggctgcagga ctgggcctgt 1650 gctcattgat cggaatttcc tttaacgctg caacaactca ggttttgcca 1700 tttctcgctc ttggtgttgg tgtggatgat gtttttcttc tggcccacgc 1750 cttcagtgaa acaggacaga ataaaagaat cccttttgag gacaggaccg 1800 gggagtgcct gaagcgcaca ggagccagcg tggccctcac gtccatcagc 1850 aatgtcacag ccttcttcat ggccgcgtta atcccaattc ccgctctgcg 1900 ggcgttctcc ctccaggcag cggtagtagt ggtgttcaat tttgccatgg 1950 ttctgctcat ttttcctgca attctcagca tggatttata tcgacgcgag 2000 gacaggagac tggatatttt ctgctgtttt acaagcccct gcgtcagcag 2050 agtgattcag gttgaacctc aggcctacac cgacacacac gacaataccc 2100 gctacagccc cccacctccc tacagcagcc acagctttgc ccatgaaacg 2150 cagattacca tgcagtccac tgtccagctc cgcacggagt acgaccccca 2200 cacgcacgtg tactacacca ccgctgagcc gcgctccgag atctctgtgc 2250 agcccgtcac cgtgacacag gacaccctca gctgccagag cccagagagc 2300 accagctcca caagggacct gctctcccag ttctccgact ccagcctcca 2350 ctgcctcgag cccccctgta cgaagtggac actctcatct tttgctgaga 2400 agcactatgc tcctttcctc ttgaaaccaa aagccaaggt agtggtgatc 2450 ttcctttttc tgggcttgct gggggtcagc ctttatggca ccacccgagt 2500 gagagacggg ctggacctta cggacattgt acctcgggaa accagagaat 2550 atgactttat tgctgcacaa ttcaaatact tttctttcta caacatgtat 2600 atagtcaccc agaaagcaga ctacccgaat atccagcact tactttacga 2650 cctacacagg agtttcagta acgtgaagta tgtcatgttg gaagaaaaca 2700 aacagcttcc caaaatgtgg ctgcactact tcagagactg gcttcaggga 2750 cttcaggatg catttgacag tgactgggaa accgggaaaa tcatgccaaa 2800 caattacaag aatggatcag acgatggagt ccttgcctac aaactcctgg 2850 tgcaaaccgg cagccgcgat aagcccatcg acatcagcca gttgactaaa 2900 cagcgtctgg tggatgcaga tggcatcatt aatcccagcg ctttctacat 2950 ctacctgacg gcttgggtca gcaacgaccc cgtcgcgtat gctgcctccc 3000 aggccaacat ccggccacac cgaccagaat gggtccacga caaagccgac 3050 tacatgcctg aaacaaggct gagaatcccg gcagcagagc ccatcgagta 3100 tgcccagttc cctttctacc tcaacggctt gcgggacacc tcagactttg 3150 tggaggcaat tgaaaaagta aggaccatct gcagcaacta tacgagcctg 3200 gggctgtcca gttaccccaa cggctacccc ttcctcttct gggagcagta 3250 catcggcctc cgccactggc tgctgctgtt catcagcgtg gtgttggcct 3300 gcacattcct cgtgtgcgct gtcttccttc tgaacccctg gacggccggg 3350 atcattgtga tggtcctggc gctgatgacg gtcgagctgt tcggcatgat 3400 gggcctcatc ggaatcaagc tcagtgccgt gcccgtggtc atcctgatcg 3450 cttctgttgg cataggagtg gagttcaccg ttcacgttgc tttggccttt 3500 ctgacggcca tcggcgacaa gaaccgcagg gctgtgcttg ccctggagca 3550 catgtttgca cccgtcctgg atggcgccgt gtccactctg ctgggagtgc 3600 tgatgctggc gggatctgag ttcgacttca ttgtcaggta tttctttgct 3650 gtgctggcga tcctcaccat cctcggcgtt ctcaatgggc tggttttgct 3700 tcccgtgctt ttgtctttct ttggaccata tcctgaggtg tctccagcca 3750 acggcttgaa ccgcctgccc acaccctccc ctgagccacc ccccagcgtg 3800 gtccgcttcg ccatgccgcc cggccacacg cacagcgggt ctgattcctc 3850 cgactcggag tatagttccc agacgacagt gtcaggcctc agcgaggagc 3900 ttcggcacta cgaggcccag cagggcgcgg gaggccctgc ccaccaagtg 3950 atcgtggaag ccacagaaaa ccccgtcttc gcccactcca ctgtggtcca 4000 tcccgaatcc aggcatcacc caccctcgaa cccgagacag cagccccacc 4050 tggactcagg gtccctgcct cccggacggc aaggccagca gccccgcagg 4100 gaccccccca gagaaggctt gtggccaccc ctctacagac cgcgcagaga 4150 cgcttttgaa atttctactg aagggcattc tggccctagc aatagggccc 4200 gctggggccc tcgcggggcc cgttctcaca accctcggaa cccagcgtcc 4250 actgccatgg gcagctccgt gcccggctac tgccagccca tcaccactgt 4300 gacggcttct gcctccgtga ctgtcgccgt gcacccgccg cctgtccctg 4350 ggcctgggcg gaacccccga gggggactct gcccaggcta ccctgagact 4400 gaccacggcc tgtttgagga cccccacgtg cctttccacg tccggtgtga 4450 gaggagggat tcgaaggtgg aagtcattga gctgcaggac gtggaatgcg 4500 aggagaggcc ccggggaagc agctccaact gagggtgatt aaaatctgaa 4550 gcaaagaggc caaagattgg aaacccccca cccccacctc tttccagaac 4600 tgcttgaaga gaactggttg gagttatgga aaagatgccc tgtgccagga 4650 cagcagttca ttgttactgt aaccgattgt attattttgt taaatatttc 4700 tataaatatt taagagatgt acacatgtgt aatataggaa ggaaggatgt 4750 aaagtggtat gatctggggc ttctccactc ctgccccaga gtgtggaggc 4800 cacagtgggg cctctccgta tttgtgcatt gggctccgtg ccacaaccaa 4850 gcttcattag tcttaaattt cagcatatgt tgctgctgct taaatattgt 4900 ataatttact tgtataattc tatgcaaata ttgcttatgt aataggatta 4950 ttttgtaaag gtttctgttt aaaatatttt aaatttgcat atcacaaccc 5000 tgtggtagta tgaaatgtta ctgttaactt tcaaacacgc tatgcgtgat 5050 aatttttttg tttaatgagc agatatgaag aaagcacgtt aatcctggtg 5100 gcttctctag gtgtcgttgt gtgcggtcct cttgtttggc tgtgcgtgtg 5150 aacacgtgtg tgagttcacc atgtactgta ctgtgatttt ttttttgtct 5200 tgttttgttt ctctacactg tctgtaacct gtagtaggct ctgacctagt 5250 caggctggaa gcgtcaggat atcttttctt cgtgctggtg agggctggcc 5300 ctaaacatcc acctaatcct ttcaaatcag cccggcaaaa gctagactct 5350 cctcgtgtct acggcatctc ttatgatcat tggctgccat ccaggacccc 5400 aatttgtgct tcagggggat aatctccttc tctcggatca ttgtgatgga 5450 tgctggaacc tcagggtatg gagctcacat cagttcatca tggtgggtgt 5500 tagagaattc ggtgacatgc ctagtgctga gccttggctg ggccatgaga 5550 gtctgtatac tctaaaaagc atgcagcatg gtgcccctct tctgaccaac 5600 acacacacga cccctccccc aacaccccca aattcaagag tggatgtggc 5650 cctgtcacag gtagaaaaac ctatttagtt aattctttct tggcccacag 5700 tctcccagaa atgatgtttt gagtccctat agtttaaact ccctctctta 5750 aatggagcag ctggttgagg ctttctagat ctgtttgcat cttctttaaa 5800 actaagtggt gagcatgcat tgtggtgtag aggcaggcat tatgtaggat 5850 aagagctccg gggggattct tcatgcacca gtgtttaggg tacgtgcttc 5900 ctaagtaaat ccaaacattg tctccatcct ccccgtcatt agtgctcttt 5950 caatgtgatg tgggaaagca ggaggatgga cacaccccac tgaaagatgt 6000 aggcaggggc aggtctctca accaggcata tttttaaaag ttgcttctgt 6050 actggttctc ttcttttgct ctgaggtgtg ggctccctca tctcgtaacc 6100 agagaccagc acatgtcagg gaagcaccca gtgtcggctc cccatccaaa 6150 tccacaccag caccttgtta cagacaagaa gtcagaggaa agggcggggt 6200 ccctgcaggg ctgaagccta agctactgtg aggcgctcac gagtggcagc 6250 tcctgttact cccttttaaa ttacctggga aatcttaaca gaaaggtaat 6300 gggcccccag aaatacccac agcatagtga cctcagaccc tgatactcac 6350 cacaaaactt ttaagatgct gattgggagc cgcttgtggc tgctgggtgt 6400 gtgtgtgtgt gtgtgcgtgc gtgcgtgtgt gtgtgtctct gctggggacc 6450 ctggccaccc ccctgctgct gtcttggtgc ctgtcaccca catggtctgc 6500 catcctaaca cccagctctg ctcagaaaac gtcctgcgtg gaggagggat 6550 gatgcagaat tctgaagtcg acttccctct ggctcctggc gtgccctcgc 6600 tcccttcctg agcccagctc gtgttgcgcc ggaggctgcg cggcccctga 6650 tttctgcatg gtgtagaact ttctccaata gtcacattgg caaagggaga 6700 actggggtgg gcggggggtg gggctggcag ggaattagaa tttctctctc 6750 tcttttaata gttttatttt gtctgtcctg tttgttcatt tggatgtttt 6800 aatttttaaa aaaaaaaaaa aaaaa 6825 ggctggcgtc ctgctggttg cactgtcagt ggctgcagga ctgggcctgt 1650 gctcattgat cggaatttcc tttaacgctg ggttttgcca caacaactca 1700 tttctcgctc ttggtgttgg tgtggatgat gtttttcttc tggcccacgc 1750 acaggacaga cttcagtgaa ataaaagaat cccttttgag gacaggaccg 1800 gaagcgcaca gggagtgcct ggagccagcg tggccctcac gtccatcagc 1850 aatgtcacag ccttcttcat ggccgcgtta atcccaattc ccgctctgcg 1900 ggcgttctcc ctccaggcag cggtagtagt ggtgttcaat tttgccatgg 1950 ttttcctgca ttctgctcat attctcagca tggatttata tcgacgcgag 2000 gacaggagac tggatatttt ctgctgtttt acaagcccct gcgtcagcag 2050 agtgattcag gttgaacctc aggcctacac cgacacacac gacaataccc 2100 gctacagccc cccacctccc tacagcagcc acagctttgc ccatgaaacg 2150 cagattacca tgcagtccac tgtccagctc cgcacggagt acgaccccca 2200 tactacacca cacgcacgtg ccgctgagcc gcgctccgag atctctgtgc 2250 agcccgtcac cgtgacacag gacaccctca gctgccagag cccagagagc 2300 accagctcca caagggacct gctctcccag ttctccgact ccagcctcca 2350 ctgcctcgag cccccctgta cgaagtggac actctcatct tttgctgaga 2400 ttg agcactatgc tcctttcctc aaaccaa aagccaaggt agtggtgatc 2450 ttcctttttc tgggcttgct gggggtcagc ctttatggca ccacccgagt 2500 gagagacggg ctggacctta cggacattgt acctcgggaa accagagaat 2550 atgactttat tgctgcacaa ttcaaatact tttctttcta caacatgtat 2600 atagtcaccc agaaagcaga ctacccgaat atccagcact tactttacga 2650 agtttcagta cctacacagg tgtcatgttg acgtgaagta gaagaaaaca 2700 aacagcttcc caaaatgtgg ctgcactact tcagagactg gcttcaggga 2750 cttcaggatg catttgacag tgactgggaa accgggaaaa tcatgccaaa 2800 caattacaag aatggatcag acgatggagt ccttgcctac aaactcctgg 2850 tgcaaaccgg cagccgcgat aagcccatcg gttgactaaa acatcagcca 2900 cagcgtctgg tggatgcaga tggcatcatt aatcccagcg ctttctacat 2950 ctacctgacg gcttgggtca gcaacgaccc cgtcgcgtat gctgcctccc 3000 aggccaacat ccggccacac cgaccagaat gggtccacga caaagccgac 3050 tacatgcctg aaacaaggct gagaatcccg gcagcagagc ccatcgagta 3100 tgcccagttc cctttctacc tcaacggctt gcgggacacc tcagactttg 3150 tggaggcaat tgaaaaagta aggaccatct gcagcaacta tacgagcctg 3200 gttaccccaa gggctgtcca cggctacccc ttcctcttct gggag ledder 3250 catcggcctc cgccactggc tgctgctgtt catcagcgtg gtgttggcct 3300 gcacattcct cgtgtgcgct gtcttccttc tgaacccctg gacggccggg 3350 atcattgtga tggtcctggc gctgatgacg gtcgagctgt tcggcatgat 3400 gggcctcatc ggaatcaagc tcagtgccgt gcccgtggtc atcctgatcg 3450 cttctgttgg cataggagtg gagttcaccg ttcacgttgc tttggccttt 3500 tcggcgacaa ctgacggcca gaaccgcagg gctgtgcttg ccctggagca 3550 catgtttgca cccgtcctgg atggcgccgt gtccactctg ctgggagtgc 3600 tgatgctggc gggatctgag ttcgacttca ttgtcaggta tttctttgct 3650 gtgctggcga tcctcaccat cctcggcgtt ctcaatgggc tggttttgct 3700 tcccgtgctt ttgtctttct ttggaccata tcctgaggtg tctccagcca 3750 acggcttgaa ccgcctgccc acaccctccc ctgagccacc ccccagcgtg 3800 gtccgcttcg ccatgccgcc cggccacacg cacagcgggt ctgattcctc 3850 cgactcggag tatagttccc agacgacagt gtcaggcctc agcgaggagc 3900 ttcggcacta cgaggcccag cagggcgcgg gaggccctgc ccaccaagtg 3950 ccacagaaaa atcgtggaag gcccactcca ccccgtcttc ctgtggtcca 4000 tcccgaatcc aggcatcacc caccctcgaa cccgagacag cagccccacc 4050 tggactcagg g tccctgcct cccggacggc aaggccagca gccccgcagg 4100 gaccccccca gagaaggctt gtggccaccc ctctacagac cgcgcagaga 4150 cgcttttgaa atttctactg aagggcattc tggccctagc aatagggccc 4200 gctggggccc tcgcggggcc cgttctcaca accctcggaa cccagcgtcc 4250 actgccatgg gcagctccgt gcccggctac tgccagccca tcaccactgt 4300 gacggcttct gcctccgtga ctgtcgccgt gcacccgccg cctgtccctg 4350 ggcctgggcg gaacccccga gggggactct gcccaggcta ccctgagact 4400 gaccacggcc tgtttgagga cccccacgtg cctttccacg tccggtgtga 4450 gaggagggat tcgaaggtgg aagtcattga gctgcaggac gtggaatgcg 4500 aggagaggcc ccggggaagc agctccaact gagggtgatt aaaatctgaa 4550 gcaaagaggc caaagattgg aaacccccca cccccacctc tttccagaac 4600 gaactggttg tgcttgaaga aaagatgccc gagttatgga tgtgccagga 4650 cagcagttca ttgttactgt aaccgattgt attattttgt taaatatttc 4700 tataaatatt taagagatgt acacatgtgt aatataggaa ggaaggatgt 4750 aaagtggtat gatctggggc ttctccactc ctgccccaga gtgtggaggc 4800 cacagtgggg cctctccgta tttgtgcatt gggctccgtg ccacaaccaa 4850 gcttcattag tcttaaattt cagcatatgt tgc tgctgct taaatattgt 4900 ataatttact tgtataattc tatgcaaata ttgcttatgt aataggatta 4950 ttttgtaaag gtttctgttt aaaatatttt aaatttgcat atcacaaccc 5000 tgaaatgtta tgtggtagta ctgttaactt tcaaacacgc tatgcgtgat 5050 aatttttttg tttaatgagc agatatgaag aaagcacgtt aatcctggtg 5100 gcttctctag gtgtcgttgt gtgcggtcct cttgtttggc tgtgcgtgtg 5150 aacacgtgtg tgagttcacc atgtactgta ctgtgatttt ttttttgtct 5200 tgttttgttt ctctacactg tctgtaacct gtagtaggct ctgacctagt 5250 caggctggaa gcgtcaggat atcttttctt cgtgctggtg agggctggcc 5300 ctaaacatcc acctaatcct ttcaaatcag cccggcaaaa gctagactct 5350 cctcgtgtct acggcatctc ttatgatcat tggctgccat ccaggacccc 5400 aatttgtgct tcagggggat aatctccttc tctcggatca ttgtgatgga 5450 tgctggaacc tcagggtatg gagctcacat cagttcatca tggtgggtgt 5500 tagagaattc ggtgacatgc ctagtgctga gccttggctg ggccatgaga 5550 gtctgtatac tctaaaaagc atgcagcatg gtgcccctct tctgaccaac 5600 acacacacga cccctccccc aacaccccca aattcaagag tggatgtggc 5650 cctgtcacag gtagaaaaac ctatttagtt aattctttct tggcccacag 5700 tctcccagaa atgatgtttt gagtccctat agtttaaact ccctctctta 5750 aatggagcag ctggttgagg ctttctagat ctgtttgcat cttctttaaa 5800 actaagtggt gagcatgcat tgtggtgtag aggcaggcat tatgtaggat 5850 aagagctccg gggggattct tcatgcacca gtgtttaggg tacgtgcttc 5900 ctaagtaaat ccaaacattg tctccatcct ccccgtcatt agtgctcttt 5950 tgggaaagca caatgtgatg ggaggatgga cacaccccac tgaaagatgt 6000 aggtctctca aggcaggggc accaggcata tttttaaaag ttgcttctgt 6050 actggttctc ttcttttgct ctgaggtgtg ggctccctca tctcgtaacc 6100 agagaccagc acatgtcagg gaagcaccca gtgtcggctc cccatccaaa 6150 caccttgtta tccacaccag cagacaagaa gtcagaggaa agggcggggt 6200 ccctgcaggg ctgaagccta agctactgtg aggcgctcac gagtggcagc 6250 cccttttaaa tcctgttact ttacctggga aatcttaaca gaaaggtaat 6300 gggcccccag aaatacccac agcatagtga cctcagaccc tgatactcac 6350 cacaaaactt ttaagatgct gattgggagc cgcttgtggc tgctgggtgt 6400 gtgtgtgtgt gtgtgcgtgc gtgcgtgtgt gtgtgtctct gctggggacc 6450 ctggccaccc ccctgctgct gtcttggtgc ctgtcaccca catggtctgc 6500 catcctaaca cccagctctg ct cagaaaac gtcctgcgtg gaggagggat 6550 gatgcagaat tctgaagtcg acttccctct ggctcctggc gtgccctcgc 6600 tcccttcctg agcccagctc gtgttgcgcc ggaggctgcg cggcccctga 6650 tttctgcatg gtgtagaact ttctccaata gtcacattgg caaagggaga 6700 actggggtgg gcggggggtg gggctggcag ggaattagaa tttctctctc 6750 tcttttaata gttttatttt gtctgtcctg tttgttcatt tggatgtttt aaaaaaaaaa 6800 aaaaa 6825 aatttttaaa

<210> 33 <210> 33

<211> 4740 <211> 4740

<212> ADN <212> DNA

<213> Homo sapiens <213> Homo sapiens

<400> 33<400> 33

ttccggtttt tctcagggga cgttgaaatt atttttgtaa cgggagtcgg 50 gagaggacgg ggcgtgcccc gcgtgcgcgc gcgtcgtcct ccccggcgct 100 cctccacagc tcgctggctc ccgccgcgga aaggcgtcat gccgcccaaa 150 accccccgaa aaacggccgc caccgccgcc gctgccgccg cggaaccccc 200 ggcaccgccg ccgccgcccc ctcctgagga ggacccagag caggacagcg 250 gcccggagga cctgcctctc gtcaggcttg agtttgaaga aacagaagaa 300 cctgatttta ctgcattatg tcagaaatta aagataccag atcatgtcag 350 agagagagct tggttaactt gggagaaagt ttcatctgtg gatggagtat 400 tgggaggtta tattcaaaag aaaaaggaac tgtggggaat ctgtatcttt 450 attgcacgag ttgacctaga tgagatgtcg ttcactttac tgagctacag 500 aaaaacatac gaaatcagtg tccataaatt ctttaactta ctaaaagaaa 550 ttgataccag taccaaagtt gataatgcta tgtcaagact gttgaagaag 600 tatgatgtat tgtttgcact cttcagcaaa ttggaaagga catgtgaact 650 tatatatttg acacaaccca gcagttcgat atctactgaa ataaattctg 700 cattggtgct aaaagtttct tggatcacat ttttattagc taaaggggaa 750 gtattacaaa tggaagatga tctggtgatt tcatttcagt taatgctatg 800 tgtccttgac tattttatta aactctcacc tcccatgttg ctcaaagaac 850 catataaaac agctgttata cccattaatg gttcacctcg aacacccagg 900 cgaggtcaga acaggagtgc acggatagca aaacaactag aaaatgatac 950 aagaattatt gaagttctct gtaaagaaca tgaatgtaat atagatgagg 1000 tgaaaaatgt ttatttcaaa aattttatac cttttatgaa ttctcttgga 1050 cttgtaacat ctaatggact tccagaggtt gaaaatcttt ctaaacgata 1100 cgaagaaatt tatcttaaaa ataaagatct agatcgaaga ttatttttgg 1150 atcatgataa aactcttcag actgattcta tagacagttt tgaaacacag 1200 agaacaccac gaaaaagtaa ccttgatgaa gaggtgaata taattcctcc 1250 acacactcca gttaggactg ttatgaacac tatccaacaa ttaatgatga 1300 ttttaaattc tgcaagtgat caaccttcag aaaatctgat ttcctatttt 1350 aacaactgca cagtgaatcc aaaagaaagt atactgaaaa gagtgaagga 1400 tataggatac atctttaaag agaaatttgc taaagctgtg ggacagggtt 1450 gtgtcgaaat tggatcacag cgatacaaac ttggagttcg cttgtattac 1500 cgagtaatgg aatccatgct taaatcagaa gaagaacgat tatccattca 1550 aaattttagc aaacttctga atgacaacat ttttcatatg tctttattgg 1600 cgtgcgctct tgaggttgta atggccacat atagcagaag tacatctcag 1650 aatcttgatt ctggaacaga tttgtctttc ccatggattc tgaatgtgct 1700 taatttaaaa gcctttgatt tttacaaagt gatcgaaagt tttatcaaag 1750 cagaaggcaa cttgacaaga gaaatgataa aacatttaga acgatgtgaa 1800 catcgaatca tggaatccct tgcatggctc tcagattcac ctttatttga 1850 tcttattaaa caatcaaagg accgagaagg accaactgat caccttgaat 1900 ctgcttgtcc tcttaatctt cctctccaga ataatcacac tgcagcagat 1950 atgtatcttt ctcctgtaag atctccaaag aaaaaaggtt caactacgcg 2000 tgtaaattct actgcaaatg cagagacaca agcaacctca gccttccaga 2050 cccagaagcc attgaaatct acctctcttt cactgtttta taaaaaagtg 2100 tatcggctag cctatctccg gctaaataca ctttgtgaac gccttctgtc 2150 tgagcaccca gaattagaac atatcatctg gacccttttc cagcacaccc 2200 tgcagaatga gtatgaactc atgagagaca ggcatttgga ccaaattatg 2250 atgtgttcca tgtatggcat atgcaaagtg aagaatatag accttaaatt 2300 caaaatcatt gtaacagcat acaaggatct tcctcatgct gttcaggaga 2350 cattcaaacg tgttttgatc aaagaagagg agtatgattc tattatagta 2400 ttctataact cggtcttcat gcagagactg aaaacaaata ttttgcagta 2450 tgcttccacc aggcccccta ccttgtcacc aatacctcac attcctcgaa 2500 gcccttacaa gtttcctagt tcacccttac ggattcctgg agggaacatc 2550 tatatttcac ccctgaagag tccatataaa atttcagaag gtctgccaac 2600 accaacaaaa atgactccaa gatcaagaat cttagtatca attggtgaat 2650 cattcgggac ttctgagaag ttccagaaaa taaatcagat ggtatgtaac 2700 agcgaccgtg tgctcaaaag aagtgctgaa ggaagcaacc ctcctaaacc 2750 actgaaaaaa ctacgctttg atattgaagg atcagatgaa gcagatggaa 2800 gtaaacatct cccaggagag tccaaatttc agcagaaact ggcagaaatg 2850 acttctactc gaacacgaat gcaaaagcag aaaatgaatg atagcatgga 2900 tacctcaaac aaggaagaga aatgaggatc tcaggacctt ggtggacact 2950 gtgtacacct ctggattcat tgtctctcac agatgtgact gtataacttt 3000 cccaggttct gtttatggcc acatttaata tcttcagctc tttttgtgga 3050 tataaaatgt gcagatgcaa ttgtttgggt gagtcctaag ccacttgaaa 3100 tgttagtcat tgttatttat acaagattga aaatcttgtg taaatcctgc 3150 catttaaaaa gttgtagcag attgtttcct cttccaaagt aaaattgctg 3200 tgctttatgg atagtaagaa tggccctaga gtgggagtcc tgataaccca 3250 ggcctgtctg actactttgc cttcttttgt agcatatagg tgatgtttgc 3300 tcttgttttt attaatttat atgtatattt ttttaattta acatgaacac 3350 ccttagaaaa tgtgtcctat ctatcttcca aatgcaattt gattgactgc 3400 ccattcacca aaattatcct gaactcttct gcaaaaatgg atattattag 3450 aaattagaaa aaaattacta attttacaca ttagatttta ttttactatt 3500 ggaatctgat atactgtgtg cttgttttat aaaattttgc ttttaattaa 3550 ataaaagctg gaagcaaagt ataaccatat gatactatca tactactgaa 3600 acagatttca tacctcagaa tgtaaaagaa cttactgatt attttcttca 3650 tccaacttat gtttttaaat gaggattatt gatagtactc ttggttttta 3700 taccattcag atcactgaat ttataaagta cccatctagt acttgaaaaa 3750 gtaaagtgtt ctgccagatc ttaggtatag aggaccctaa cacagtatat 3800 cccaagtgca ctttctaatg tttctgggtc ctgaagaatt aagatacaaa 3850 ttaattttac tccataaaca gactgttaat tataggagcc ttaatttttt 3900 tttcatagag atttgtctaa ttgcatctca aaattattct gccctcctta 3950 atttgggaag gtttgtgttt tctctggaat ggtacatgtc ttccatgtat 4000 cttttgaact ggcaattgtc tatttatctt ttattttttt aagtcagtat 4050 ggtctaacac tggcatgttc aaagccacat tatttctagt ccaaaattac 4100 aagtaatcaa gggtcattat gggttaggca ttaatgtttc tatctgattt 4150 tgtgcaaaag cttcaaatta aaacagctgc attagaaaaa gaggcgcttc 4200 tcccctcccc tacacctaaa ggtgtattta aactatcttg tgtgattaac 4250 ttatttagag atgctgtaac ttaaaatagg ggatatttaa ggtagcttca 4300 gctagctttt aggaaaatca ctttgtctaa ctcagaatta tttttaaaaa 4350 gaaatctggt cttgttagaa aacaaaattt tattttgtgc tcatttaagt 4400 ttcaaactta ctattttgac agttattttg ataacaatga cactagaaaa 4450 cttgactcca tttcatcatt gtttctgcat gaatatcata caaatcagtt 4500 agtttttagg tcaagggctt actatttctg ggtcttttgc tactaagttc 4550 acattagaat tagtgccaga attttaggaa cttcagagat cgtgtattga 4600 gatttcttaa ataatgcttc agatattatt gctttattgc ttttttgtat 4650 tggttaaaac tgtacattta aaattgctat gttactattt tctacaatta 4700 atagtttgtc tattttaaaa taaattagtt gttaagagtc 4740 ttccggtttt tctcagggga cgttgaaatt atttttgtaa cgggagtcgg 50 gagaggacgg ggcgtgcccc gcgtgcgcgc gcgtcgtcct ccccggcgct 100 cctccacagc tcgctggctc ccgccgcgga aaggcgtcat gccgcccaaa 150 accccccgaa aaacggccgc caccgccgcc gctgccgccg cggaaccccc 200 ggcaccgccg ccgccgcccc ctcctgagga ggacccagag caggacagcg 250 gcccggagga cctgcctctc gtcaggcttg agtttgaaga aacagaagaa 300 cctgatttta ctgcattatg tcagaaatta aagataccag atcatgtcag 350 agagagagct tggttaactt gggagaaagt ttcatctgtg gatggagtat 400 tgggaggtta tattcaaaag aaaaaggaac tgtggggaat ctgtatcttt 450 attgcacgag ttgacctaga tgagatgtcg ttcactttac tgagctacag 500 aaaaacatac gaaatcagtg tccataaatt ctttaactta ctaaaagaaa 550 ttgataccag taccaaagtt gataatgcta tgtcaagact gttgaagaag 600 tatgatgtat tgtttgcact cttcagcaaa ttggaaagga catgtgaact 650 tatatatttg acacaaccca gcagttcgat atctactgaa ataaattctg 700 cattggtgct aaaagtttct tggatcacat ttttattagc taaaggggaa 750 tggaagatga gtattacaaa tctggtgatt tcatttcagt taatgctatg 800 tgtccttgac tattttatta aactctcacc tcccatgtt g ctcaaagaac 850 catataaaac agctgttata cccattaatg gttcacctcg aacacccagg 900 cgaggtcaga acaggagtgc acggatagca aaacaactag aaaatgatac 950 aagaattatt gaagttctct gtaaagaaca tgaatgtaat atagatgagg 1000 tgaaaaatgt ttatttcaaa aattttatac cttttatgaa ttctcttgga 1050 cttgtaacat ctaatggact tccagaggtt gaaaatcttt ctaaacgata 1100 cgaagaaatt tatcttaaaa ataaagatct agatcgaaga ttatttttgg 1150 atcatgataa aactcttcag actgattcta tagacagttt tgaaacacag 1200 gaaaaagtaa agaacaccac ccttgatgaa gaggtgaata taattcctcc 1250 acacactcca gttaggactg ttatgaacac tatccaacaa ttaatgatga 1300 ttttaaattc tgcaagtgat caaccttcag aaaatctgat ttcctatttt 1350 cagtgaatcc aacaactgca aaaagaaagt atactgaaaa gagtgaagga 1400 tataggatac atctttaaag agaaatttgc taaagctgtg ggacagggtt 1450 gtgtcgaaat tggatcacag cgatacaaac ttggagttcg cttgtattac 1500 cgagtaatgg aatccatgct taaatcagaa gaagaacgat tatccattca 1550 aaattttagc aaacttctga atgacaacat ttttcatatg tctttattgg 1600 cgtgcgctct tgaggttgta atggccacat atagcagaag tacatctcag 1650 aatcttga tt ctggaacaga tttgtctttc ccatggattc tgaatgtgct 1700 taatttaaaa gcctttgatt tttacaaagt gatcgaaagt tttatcaaag 1750 cttgacaaga cagaaggcaa aacatttaga gaaatgataa acgatgtgaa 1800 catcgaatca tggaatccct tgcatggctc tcagattcac ctttatttga 1850 tcttattaaa caatcaaagg accgagaagg accaactgat caccttgaat 1900 ctgcttgtcc tcttaatctt cctctccaga ataatcacac tgcagcagat 1950 atgtatcttt ctcctgtaag atctccaaag aaaaaaggtt caactacgcg 2000 tgtaaattct actgcaaatg cagagacaca agcaacctca gccttccaga 2050 cccagaagcc attgaaatct acctctcttt cactgtttta taaaaaagtg 2100 tatcggctag cctatctccg gctaaataca ctttgtgaac gccttctgtc 2150 tgagcaccca gaattagaac atatcatctg gacccttttc cagcacaccc 2200 gtatgaactc tgcagaatga atgagagaca ggcatttgga ccaaattatg 2250 atgtgttcca tgtatggcat atgcaaagtg aagaatatag accttaaatt 2300 caaaatcatt gtaacagcat acaaggatct tcctcatgct gttcaggaga 2350 cattcaaacg tgttttgatc aaagaagagg agtatgattc tattatagta 2400 ttctataact cggtcttcat gcagagactg ttttgcagta aaaacaaata 2450 tgcttccacc aggcccccta ccttgtcacc aatacctcac attcctcgaa 2500 gcccttacaa gtttcctagt tcacccttac ggattcctgg agggaacatc 2550 tatatttcac ccctgaagag tccatataaa atttcagaag gtctgccaac 2600 atgactccaa accaacaaaa cttagtatca gatcaagaat attggtgaat 2650 cattcgggac ttctgagaag ttccagaaaa taaatcagat ggtatgtaac 2700 agcgaccgtg tgctcaaaag aagtgctgaa ggaagcaacc ctcctaaacc 2750 actgaaaaaa ctacgctttg atattgaagg atcagatgaa gcagatggaa 2800 gtaaacatct cccaggagag tccaaatttc agcagaaact ggcagaaatg 2850 acttctactc gaacacgaat gcaaaagcag aaaatgaatg atagcatgga 2900 tacctcaaac aaggaagaga aatgaggatc tcaggacctt ggtggacact 2950 gtgtacacct ctggattcat tgtctctcac agatgtgact gtataacttt 3000 cccaggttct gtttatggcc acatttaata tcttcagctc tttttgtgga 3050 tataaaatgt gcagatgcaa ttgtttgggt gagtcctaag ccacttgaaa 3100 tgttagtcat tgttatttat acaagattga aaatcttgtg taaatcctgc 3150 catttaaaaa gttgtagcag attgtttcct cttccaaagt aaaattgctg 3200 tgctttatgg atagtaagaa tggccctaga gtgggagtcc tgataaccca 3250 ggcctgtctg actactttgc cttcttttgt agcatatagg tgatgtttgc 3 300 tcttgttttt attaatttat atgtatattt ttttaattta acatgaacac 3350 ccttagaaaa tgtgtcctat ctatcttcca aatgcaattt gattgactgc 3400 ccattcacca aaattatcct gaactcttct gcaaaaatgg atattattag 3450 aaaattacta aaattagaaa ttagatttta attttacaca ttttactatt 3500 ggaatctgat atactgtgtg cttgttttat aaaattttgc ttttaattaa 3550 ataaaagctg gaagcaaagt ataaccatat gatactatca tactactgaa 3600 tacctcagaa acagatttca tgtaaaagaa attttcttca cttactgatt 3650 tccaacttat gtttttaaat gaggattatt gatagtactc ttggttttta 3700 taccattcag atcactgaat ttataaagta cccatctagt acttgaaaaa 3750 gtaaagtgtt ctgccagatc ttaggtatag aggaccctaa cacagtatat 3800 cccaagtgca ctttctaatg tttctgggtc ctgaagaatt aagatacaaa 3850 tccataaaca ttaattttac gactgttaat tataggagcc ttaatttttt 3900 atttgtctaa tttcatagag ttgcatctca aaattattct gccctcctta 3950 atttgggaag gtttgtgttt tctctggaat ggtacatgtc ttccatgtat 4000 cttttgaact ggcaattgtc tatttatctt ttattttttt aagtcagtat 4050 ggtctaacac tggcatgttc aaagccacat tatttctagt ccaaaattac 4100 aagtaatcaa gggtcatt at gggttaggca ttaatgtttc tatctgattt 4150 tgtgcaaaag cttcaaatta aaacagctgc attagaaaaa gaggcgcttc 4200 tcccctcccc tacacctaaa ggtgtattta aactatcttg tgtgattaac 4250 ttatttagag atgctgtaac ttaaaatagg ggtagcttca ggatatttaa 4300 aggaaaatca gctagctttt ctttgtctaa ctcagaatta tttttaaaaa 4350 gaaatctggt cttgttagaa aacaaaattt tattttgtgc tcatttaagt 4400 ttcaaactta ctattttgac agttattttg ataacaatga cactagaaaa 4450 cttgactcca tttcatcatt gtttctgcat gaatatcata caaatcagtt 4500 agtttttagg tcaagggctt actatttctg ggtcttttgc tactaagttc 4550 tagtgccaga acattagaat cttcagagat attttaggaa cgtgtattga 4600 gatttcttaa ataatgcttc agatattatt gctttattgc ttttttgtat 4650 tggttaaaac tgtacattta aaattgctat gttactattt tctacaatta 4700 atagtttgtc tattttaaaa taaattagtt gttaagagtc 4740

<210> 34 <211> 4161 <210> 34 <211> 4161

<212> ADN <212> DNA

<213> Homo sapiens <213> Homo sapiens

<400> 34 <400> 34

ccgaagcagg gcgcgcagca gcgctgagtg ccccggaacg tgcgtcgcgc 50 ccgaagcagg gcgcgcagca gcgctgagtg ccccggaacg tgcgtcgcgc 50

ccccagtgtc cgtcgcgtcc gccgcgcccc gggcggggat ggggcggcca 100 ccccagtgtc cgtcgcgtcc gccgcgcccc gggcggggat ggggcggcca 100

gactgagcgc cgcacccgcc atccagaccc gccggcccta gccgcagtcc 150 gactgagcgc cgcacccgcc atccagaccc gccggcccta gccgcagtcc 150

ctccagccgt ggccccagcg cgcacgggcg atggcgaagg cgacgtccgg 200 ctccagccgt ggccccagcg cgcacgggcg atggcgaagg cgacgtccgg 200

tgccgcgggg ctgcgtctgc tgttgctgct gctgctgccg ctgctaggca 250 tgccgcgggg ctgcgtctgc tgttgctgct gctgctgccg ctgctaggca 250

aagtggcatt gggcctctac ttctcgaggg atgcttactg ggagaagctg 300 aagtggcatt gggcctctac ttctcgaggg atgcttactg ggagaagctg 300

tatgtggacc aggcggccgg cacgcccttg ctgtacgtcc atgccctgcg 350 tatgtggacc aggcggccgg cacgcccttg ctgtacgtcc atgccctgcg 350

ggacgcccct gaggaggtgc ccagcttccg cctgggccag catctctacg 400 ggacgcccct gaggaggtgc ccagcttccg cctgggccag catctctacg 400

gcacgtaccg cacacggctg catgagaaca actggatctg catccaggag 450 gcacgtaccg cacacggctg catgagaaca actggatctg catccaggag 450

gacaccggcc tcctctacct taaccggagc ctggaccata gctcctggga 500 gacaccggcc tcctctacct taaccggagc ctggaccata gctcctggga 500

gaagctcagt gtccgcaacc gcggctttcc cctgctcacc gtctacctca 550 gaagctcagt gtccgcaacc gcggctttcc cctgctcacc gtctacctca 550

aggtcttcct gtcacccaca tcccttcgtg agggcgagtg ccagtggcca 600 aggtcttcct gtcacccaca tcccttcgtg agggcgagtg ccagtggcca 600

ggctgtgccc gcgtatactt ctccttcttc aacacctcct ttccagcctg 650 ggctgtgccc gcgtatactt ctccttcttc aacacctcct ttccagcctg 650

cagctccctc aagccccggg agctctgctt cccagagaca aggccctcct 700 cagctccctc aagccccggg agctctgctt cccagagaca aggccctcct 700

tccgcattcg ggagaaccga cccccaggca ccttccacca gttccgcctg 750 tccgcattcg ggagaaccga cccccaggca ccttccacca gttccgcctg 750

ctgcctgtgc agttcttgtg ccccaacatc agcgtggcct acaggctcct 800 ctgcctgtgc agttcttgtg ccccaacatc agcgtggcct acaggctcct 800

ggagggtgag ggtctgccct tccgctgcgc cccggacagc ctggaggtga 850 ggagggtgag ggtctgccct tccgctgcgc cccggacagc ctggaggtga 850

gcacgcgctg ggccctggac cgcgagcagc gggagaagta cgagctggtg 900 gcacgcgctg ggccctggac cgcgagcagc gggagaagta cgagctggtg 900

gccgtgtgca ccgtgcacgc cggcgcgcgc gaggaggtgg tgatggtgcc 950 gccgtgtgca ccgtgcacgc cggcgcgcgc gaggaggtgg tgatggtgcc 950

cttcccggtg accgtgtacg acgaggacga ctcggcgccc accttccccg 1000 cttcccggtg accgtgtacg acgaggacga ctcggcgccc accttccccg 1000

cgggcgtcga caccgccagc gccgtggtgg agttcaagcg gaaggaggac 1050 cgggcgtcga caccgccagc gccgtggtgg agttcaagcg gaaggaggac 1050

accgtggtgg ccacgctgcg tgtcttcgat gcagacgtgg tacctgcatc 1100 accgtggtgg ccacgctgcg tgtcttcgat gcagacgtgg tacctgcatc 1100

aggggagctg gtgaggcggt acacaagcac gctgctcccc ggggacacct 1150 aggggagctg gtgaggcggt acacaagcac gctgctcccc ggggacacct 1150

gggcccagca gaccttccgg gtggaacact ggcccaacga gacctcggtc 1200 gggcccagca gaccttccgg gtggaacact ggcccaacga gacctcggtc 1200

caggccaacg gcagcttcgt gcgggcgacc gtacatgact ataggctggt 1250 caggccaacg gcagcttcgt gcgggcgacc gtacatgact ataggctggt 1250

tctcaaccgg aacctctcca tctcggagaa ccgcaccatg cagctggcgg 1300 tctcaaccgg aacctctcca tctcggagaa ccgcaccatg cagctggcgg 1300

tgctggtcaa tgactcagac ttccagggcc caggagcggg cgtcctcttg 1350 tgctggtcaa tgactcagac ttccagggcc caggagcggg cgtcctcttg 1350

ctccacttca acgtgtcggt gctgccggtc agcctgcacc tgcccagtac 1400 ctccacttca acgtgtcggt gctgccggtc agcctgcacc tgcccagtac 1400

ctactccctc tccgtgagca ggagggctcg ccgatttgcc cagatcggga 1450 ctactccctc tccgtgagca ggagggctcg ccgatttgcc cagatcggga 1450

aagtctgtgt ggaaaactgc caggcattca gtggcatcaa cgtccagtac 1500 aagtctgtgt ggaaaactgc caggcattca gtggcatcaa cgtccagtac 1500

aagctgcatt cctctggtgc caactgcagc acgctagggg tggtcacctc 1550 aagctgcatt cctctggtgc caactgcagc acgctagggg tggtcacctc 1550

agccgaggac acctcgggga tcctgtttgt gaatgacacc aaggccctgc 1600 agccgaggac acctcgggga tcctgtttgt gaatgacacc aaggccctgc 1600

ggcggcccaa gtgtgccgaa cttcactaca tggtggtggc caccgaccag 1650 cagacctcta ggcaggccca ggcccagctg cttgtaacag tggaggggtc 1700 atatgtggcc gaggaggcgg gctgccccct gtcctgtgca gtcagcaaga 1750 gacggctgga gtgtgaggag tgtggcggcc tgggctcccc aacaggcagg 1800 tgtgagtgga ggcaaggaga tggcaaaggg atcaccagga acttctccac 1850 ctgctctccc agcaccaaga cctgccccga cggccactgc gatgttgtgg 1900 agacccaaga catcaacatt tgccctcagg actgcctccg gggcagcatt 1950 gttgggggac acgagcctgg ggagccccgg gggattaaag ctggctatgg 2000 cacctgcaac tgcttccctg aggaggagaa gtgcttctgc gagcccgaag 2050 acatccagga tccactgtgc gacgagctgt gccgcacggt gatcgcagcc 2100 gctgtcctct tctccttcat cgtctcggtg ctgctgtctg ccttctgcat 2150 ccactgctac cacaagtttg cccacaagcc acccatctcc tcagctgaga 2200 tgaccttccg gaggcccgcc caggccttcc cggtcagcta ctcctcttcc 2250 ggtgcccgcc ggccctcgct ggactccatg gagaaccagg tctccgtgga 2300 tgccttcaag atcctggagg atccaaagtg ggaattccct cggaagaact 2350 tggttcttgg aaaaactcta ggagaaggcg aatttggaaa agtggtcaag 2400 gcaacggcct tccatctgaa aggcagagca gggtacacca cggtggccgt 2450 gaagatgctg aaagagaacg cctccccgag tgagctgcga gacctgctgt 2500 cagagttcaa cgtcctgaag caggtcaacc acccacatgt catcaaattg 2550 tatggggcct gcagccagga tggcccgctc ctcctcatcg tggagtacgc 2600 caaatacggc tccctgcggg gcttcctccg cgagagccgc aaagtggggc 2650 ctggctacct gggcagtgga ggcagccgca actccagctc cctggaccac 2700 ccggatgagc gggccctcac catgggcgac ctcatctcat ttgcctggca 2750 gatctcacag gggatgcagt atctggccga gatgaagctc gttcatcggg 2800 acttggcagc cagaaacatc ctggtagctg aggggcggaa gatgaagatt 2850 tcggatttcg gcttgtcccg agatgtttat gaagaggatt cctacgtgaa 2900 gaggagccag ggtcggattc cagttaaatg gatggcaatt gaatcccttt 2950 ttgatcatat ctacaccacg caaagtgatg tatggtcttt tggtgtcctg 3000 ctgtgggaga tcgtgaccct agggggaaac ccctatcctg ggattcctcc 3050 tgagcggctc ttcaaccttc tgaagaccgg ccaccggatg gagaggccag 3100 acaactgcag cgaggagatg taccgcctga tgctgcaatg ctggaagcag 3150 gagccggaca aaaggccggt gtttgcggac atcagcaaag acctggagaa 3200 gatgatggtt aagaggagag actacttgga ccttgcggcg tccactccat 3250 ctgactccct gatttatgac gacggcctct cagaggagga gacaccgctg 3300 gtggactgta ataatgcccc cctccctcga gccctccctt ccacatggat 3350 tgaaaacaaa ctctatggta gaatttccca tgcatttact agattctagc 3400 accgctgtcc cctctgcact atccttcctc tctgtgatgc tttttaaaaa 3450 tgtttctggt ctgaacaaaa ccaaagtctg ctctgaacct ttttatttgt 3500 aaatgtctga ctttgcatcc agtttacatt taggcattat tgcaactatg 3550 tttttctaaa aggaagtgaa aataagtgta attaccacat tgcccagcaa 3600 cttaggatgg tagaggaaaa aacagatcag ggcggaactc tcaggggaga 3650 ccaagaacag gttgaataag gcgcttctgg ggtgggaatc aagtcatagt 3700 acttctactt taactaagtg gataaatata caaatctggg gaggtattca 3750 gttgagaaag gagccaccag caccactcag cctgcactgg gagcacagcc 3800 aggttccccc agacccctcc tgggcaggca ggtgcctctc agaggccacc 3850 cggcactggc gagcagccac tggccaagcc tcagccccag tcccagccac 3900 atgtcctcca tcaggggtag cgaggttgca ggagctggct ggccctggga 3950 ggacgcaccc ccactgctgt tttcacatcc tttcccttac ccaccttcag 4000 gacggttgtc acttatgaag tcagtgctaa agctggagca gttgcttttt 4050 gaaagaacat ggtctgtggt gctgtggtct tacaatggac agtaaatatg 4100 gttcttgcca aaactccttc ttttgtcttt gattaaatac tagaaattta 4150 aaaaaaaaaa a 4161 ggcggcccaa cttcactaca gtgtgccgaa tggtggtggc caccgaccag 1650 ggcaggccca cagacctcta ggcccagctg cttgtaacag tggaggggtc 1700 atatgtggcc gaggaggcgg gctgccccct gtcctgtgca gtcagcaaga 1750 gacggctgga gtgtgaggag tgtggcggcc tgggctcccc aacaggcagg 1800 ggcaaggaga tgtgagtgga tggcaaaggg atcaccagga acttctccac 1850 agcaccaaga ctgctctccc cctgccccga cggccactgc gatgttgtgg 1900 agacccaaga catcaacatt tgccctcagg actgcctccg gggcagcatt 1950 gttgggggac acgagcctgg ggagccccgg gggattaaag ctggctatgg 2000 cacctgcaac tgcttccctg aggaggagaa gtgcttctgc gagcccgaag 2050 acatccagga tccactgtgc gacgagctgt gccgcacggt gatcgcagcc 2100 gctgtcctct tctccttcat cgtctcggtg ctgctgtctg ccttctgcat 2150 ccactgctac cacaagtttg cccacaagcc acccatctcc tcagctgaga 2200 tgaccttccg gaggcccgcc caggccttcc cggtcagcta ctcctcttcc 2250 ggtgcccgcc ggccctcgct ggactccatg gagaaccagg tctccgtgga 2300 tgccttcaag atcctggagg atccaaagtg ggaattccct cggaagaact 2350 tggttcttgg aaaaactcta ggagaaggcg aatttggaaa agtggtcaag 2400 gcaacggcct tccatctgaa ag gcagagca gggtacacca cggtggccgt 2450 gaagatgctg aaagagaacg cctccccgag tgagctgcga gacctgctgt 2500 cagagttcaa cgtcctgaag caggtcaacc acccacatgt catcaaattg 2550 tatggggcct gcagccagga tggcccgctc ctcctcatcg tggagtacgc 2600 caaatacggc tccctgcggg gcttcctccg cgagagccgc aaagtggggc 2650 gggcagtgga ctggctacct ggcagccgca actccagctc cctggaccac 2700 ccggatgagc gggccctcac catgggcgac ctcatctcat ttgcctggca 2750 gatctcacag gggatgcagt atctggccga gatgaagctc gttcatcggg 2800 acttggcagc cagaaacatc ctggtagctg aggggcggaa gatgaagatt 2850 tcggatttcg gcttgtcccg agatgtttat gaagaggatt cctacgtgaa 2900 gaggagccag ggtcggattc cagttaaatg gatggcaatt gaatcccttt 2950 ttgatcatat ctacaccacg caaagtgatg tatggtcttt tggtgtcctg 3000 ctgtgggaga tcgtgaccct agggggaaac ccctatcctg ggattcctcc 3050 tgagcggctc ttcaaccttc tgaagaccgg ccaccggatg gagaggccag 3100 acaactgcag cgaggagatg taccgcctga tgctgcaatg ctggaagcag 3150 gagccggaca aaaggccggt gtttgcggac atcagcaaag acctggagaa 3200 gatgatggtt aagaggagag actacttgga ccttgcggcg TCCA ctccat 3250 ctgactccct gatttatgac gacggcctct cagaggagga gacaccgctg 3300 gtggactgta ataatgcccc cctccctcga gccctccctt ccacatggat 3350 ctctatggta tgaaaacaaa gaatttccca tgcatttact agattctagc 3400 accgctgtcc cctctgcact atccttcctc tctgtgatgc tttttaaaaa 3450 tgtttctggt ctgaacaaaa ccaaagtctg ctctgaacct ttttatttgt 3500 aaatgtctga ctttgcatcc agtttacatt taggcattat tgcaactatg 3550 aggaagtgaa tttttctaaa aataagtgta attaccacat tgcccagcaa 3600 cttaggatgg tagaggaaaa aacagatcag ggcggaactc tcaggggaga 3650 ccaagaacag gttgaataag gcgcttctgg ggtgggaatc aagtcatagt 3700 acttctactt taactaagtg gataaatata caaatctggg gaggtattca 3750 gttgagaaag gagccaccag caccactcag cctgcactgg gagcacagcc 3800 aggttccccc agacccctcc tgggcaggca ggtgcctctc agaggccacc 3850 cggcactggc gagcagccac tggccaagcc tcagccccag tcccagccac 3900 tcaggggtag atgtcctcca ggagctggct cgaggttgca ggccctggga 3950 ggacgcaccc ccactgctgt tttcacatcc tttcccttac ccaccttcag 4000 gacggttgtc acttatgaag tcagtgctaa agctggagca gttgcttttt 4050 gaaagaacat g gtctgtggt gctgtggtct tacaatggac agtaaatatg 4100 gttcttgcca aaactccttc ttttgtcttt gattaaatac tagaaattta 4150 aaaaaaaaaa to 4161

<210> 35 <210> 35

<211> 2346 <211> 2346

<212> ADN <212> DNA

<213> Homo sapiens <213> Homo sapiens

<400> 35<400> 35

acaaggcagc ctcgctcgag cgcaggccaa tcggctttct agctagaggg 50 tttaactcct atttaaaaag aagaaccttt gaattctaac ggctgagctc 100 ttggaagact tgggtccttg ggtcgcaggt gggagccgac gggtgggtag 150 accgtggggg atatctcagt ggcggacgag gacggcgggg acaaggggcg 200 gctggtcgga gtggcggagc gtcaagtccc ctgtcggttc ctccgtccct 250 gagtgtcctt ggcgctgcct tgtgcccgcc cagcgccttt gcatccgctc 300 ctgggcaccg aggcgccctg taggatactg cttgttactt attacagcta 350 gaggcatcat ggaccgatct aaagaaaact gcatttcagg acctgttaag 400 gctacagctc cagttggagg tccaaaacgt gttctcgtga ctcagcaatt 450 tccttgtcag aatccattac ctgtaaatag tggccaggct cagcgggtct 500 tgtgtccttc aaattcttcc cagcgcattc ctttgcaagc acaaaagctt 550 gtctccagtc acaagccggt tcagaatcag aagcagaagc aattgcaggc 600 aaccagtgta cctcatcctg tctccaggcc actgaataac acccaaaaga 650 gcaagcagcc cctgccatcg gcacctgaaa ataatcctga ggaggaactg 700 gcatcaaaac agaaaaatga agaatcaaaa aagaggcagt gggctttgga 750 agactttgaa attggtcgcc ctctgggtaa aggaaagttt ggtaatgttt 800 atttggcaag agaaaagcaa agcaagttta ttctggctct taaagtgtta 850 tttaaagctc agctggagaa agccggagtg gagcatcagc tcagaagaga 900 agtagaaata cagtcccacc ttcggcatcc taatattctt agactgtatg 950 gttatttcca tgatgctacc agagtctacc taattctgga atatgcacca 1000 cttggaacag tttatagaga acttcagaaa ctttcaaagt ttgatgagca 1050 gagaactgct acttatataa cagaattggc aaatgccctg tcttactgtc 1100 attcgaagag agttattcat agagacatta agccagagaa cttacttctt 1150 ggatcagctg gagagcttaa aattgcagat tttgggtggt cagtacatgc 1200 tccatcttcc aggaggacca ctctctgtgg caccctggac tacctgcccc 1250 ctgaaatgat tgaaggtcgg atgcatgatg agaaggtgga tctctggagc 1300 cttggagttc tttgctatga atttttagtt gggaagcctc cttttgaggc 1350 aaacacatac caagagacct acaaaagaat atcacgggtt gaattcacat 1400 tccctgactt tgtaacagag ggagccaggg acctcatttc aagactgttg 1450 aagcataatc ccagccagag gccaatgctc agagaagtac ttgaacaccc 1500 ctggatcaca gcaaattcat caaaaccatc aaattgccaa aacaaagaat 1550 cagctagcaa acagtcttag gaatcgtgca gggggagaaa tccttgagcc 1600 agggctgcca tataacctga caggaacatg ctactgaagt ttattttacc 1650 attgactgct gccctcaatc tagaacgcta cacaagaaat atttgtttta 1700 ctcagcaggt gtgccttaac ctccctattc agaaagctcc acatcaataa 1750 acatgacact ctgaagtgaa agtagccacg agaattgtgc tacttatact 1800 ggttcataat ctggaggcaa ggttcgactg cagccgcccc gtcagcctgt 1850 gctaggcatg gtgtcttcac aggaggcaaa tccagagcct ggctgtgggg 1900 aaagtgacca ctctgccctg accccgatca gttaaggagc tgtgcaataa 1950 ccttcctagt acctgagtga gtgtgtaact tattgggttg gcgaagcctg 2000 gtaaagctgt tggaatgagt atgtgattct ttttaagtat gaaaataaag 2050 atatatgtac agacttgtat tttttctctg gtggcattcc tttaggaatg 2100 ctgtgtgtct gtccggcacc ccggtaggcc tgattgggtt tctagtcctc 2150 cttaaccact tatctcccat atgagagtgt gaaaaatagg aacacgtgct 2200 ctacctccat ttagggattt gcttgggata cagaagaggc catgtgtctc 2250 agagctgtta agggcttatt tttttaaaac attggagtca tagcatgtgt 2300 gtaaacttta aatatgcaaa taaataagta tctatgtcta aaaaaa 2346 acaaggcagc ctcgctcgag cgcaggccaa tcggctttct agctagaggg 50 tttaactcct atttaaaaag aagaaccttt gaattctaac ggctgagctc 100 ttggaagact tgggtccttg ggtcgcaggt gggagccgac gggtgggtag 150 accgtggggg atatctcagt ggcggacgag gacggcgggg acaaggggcg 200 gctggtcgga gtggcggagc gtcaagtccc ctgtcggttc ctccgtccct 250 gagtgtcctt ggcgctgcct tgtgcccgcc cagcgccttt gcatccgctc 300 ctgggcaccg aggcgccctg taggatactg cttgttactt attacagcta 350 gaggcatcat ggaccgatct aaagaaaact gcatttcagg acctgttaag 400 gctacagctc cagttggagg tccaaaacgt gttctcgtga ctcagcaatt 450 tccttgtcag aatccattac ctgtaaatag tggccaggct cagcgggtct 500 tgtgtccttc aaattcttcc cagcgcattc ctttgcaagc acaaaagctt 550 gtctccagtc acaagccggt tcagaatcag aagcagaagc aattgcaggc 600 aaccagtgta cctcatcctg tctccaggcc actgaataac acccaaaaga 650 gcaagcagcc cctgccatcg gcacctgaaa ataatcctga ggaggaactg 700 agaaaaatga gcatcaaaac aagaggcagt agaatcaaaa gggctttgga 750 agactttgaa attggtcgcc ctctgggtaa aggaaagttt ggtaatgttt 800 atttggcaag agaaaagcaa agcaagttta ttctggctc t taaagtgtta 850 tttaaagctc agctggagaa agccggagtg gagcatcagc tcagaagaga 900 agtagaaata cagtcccacc ttcggcatcc taatattctt agactgtatg 950 gttatttcca tgatgctacc agagtctacc atatgcacca taattctgga 1000 cttggaacag tttatagaga acttcagaaa ctttcaaagt ttgatgagca 1050 gagaactgct acttatataa cagaattggc aaatgccctg tcttactgtc 1100 attcgaagag agttattcat agagacatta agccagagaa cttacttctt 1150 ggatcagctg gagagcttaa aattgcagat tttgggtggt cagtacatgc 1200 tccatcttcc aggaggacca ctctctgtgg caccctggac tacctgcccc 1250 ctgaaatgat tgaaggtcgg atgcatgatg agaaggtgga tctctggagc 1300 cttggagttc tttgctatga atttttagtt gggaagcctc cttttgaggc 1350 aaacacatac caagagacct acaaaagaat atcacgggtt gaattcacat 1400 tccctgactt tgtaacagag ggagccaggg acctcatttc aagactgttg 1450 aagcataatc ccagccagag gccaatgctc agagaagtac ttgaacaccc 1500 ctggatcaca gcaaattcat caaaaccatc aaattgccaa aacaaagaat 1550 acagtcttag cagctagcaa gaatcgtgca gggggagaaa tccttgagcc 1600 tataacctga agggctgcca caggaacatg ctactgaagt ttattttacc 1650 attgactg ct gccctcaatc tagaacgcta cacaagaaat atttgtttta 1700 ctcagcaggt gtgccttaac ctccctattc agaaagctcc acatcaataa 1750 acatgacact ctgaagtgaa agtagccacg agaattgtgc tacttatact 1800 ggttcataat ctggaggcaa ggttcgactg cagccgcccc gtcagcctgt 1850 gctaggcatg gtgtcttcac aggaggcaaa tccagagcct ggctgtgggg 1900 aaagtgacca ctctgccctg accccgatca gttaaggagc tgtgcaataa 1950 ccttcctagt acctgagtga gtgtgtaact tattgggttg gcgaagcctg 2000 gtaaagctgt tggaatgagt atgtgattct ttttaagtat gaaaataaag 2050 atatatgtac agacttgtat tttttctctg gtggcattcc tttaggaatg 2100 ctgtgtgtct gtccggcacc ccggtaggcc tgattgggtt tctagtcctc 2150 cttaaccact tatctcccat atgagagtgt gaaaaatagg aacacgtgct 2200 ctacctccat ttagggattt gcttgggata cagaagaggc catgtgtctc 2250 agagctgtta agggcttatt tttttaaaac attggagtca tagcatgtgt 2300 aatatgcaaa gtaaacttta tctatgtcta taaataagta aaaaaa 2346

<210> 36 <210> 36

<211> 2090 <211> 2090

<212> ADN <212> DNA

<213> Homo sapiens <213> Homo sapiens

<400> 36 <400> 36

gttggcgagg agtttcctgt ttcccccgca gcgctgagtt gaagttgagt 50 gttggcgagg agtttcctgt ttcccccgca gcgctgagtt gaagttgagt 50

gagtcactcg cgcgcacgga gcgacgacac ccccgcgcgt gcacccgctc 100 gagtcactcg cgcgcacgga gcgacgacac ccccgcgcgt gcacccgctc 100

gggacaggag ccggactcct gtgcagcttc cctcggccgc cgggggcctc 150 gggacaggag ccggactcct gtgcagcttc cctcggccgc cgggggcctc 150

cccgcgcctc gccggcctcc aggcccctcc tggctggcga gcgggcgcca 200 cccgcgcctc gccggcctcc aggcccctcc tggctggcga gcgggcgcca 200

catctggccc gcacatctgc gctgccggcc cggcgcgggg tccggagagg 250 catctggccc gcacatctgc gctgccggcc cggcgcgggg tccggagagg 250

gcgcggcgcg gagcgcagcc aggggtccgg gaaggcgccg tccgtgcgct 300 gcgcggcgcg gagcgcagcc aggggtccgg gaaggcgccg tccgtgcgct 300

gggggctcgg tctatgacga gcagcggggt ctgccatggg tcgggggctg 350 gggggctcgg tctatgacga gcagcggggt ctgccatggg tcgggggctg 350

ctcaggggcc tgtggccgct gcacatcgtc ctgtggacgc gtatcgccag 400 ctcaggggcc tgtggccgct gcacatcgtc ctgtggacgc gtatcgccag 400

cacgatccca ccgcacgttc agaagtcggt taataacgac atgatagtca 450 cacgatccca ccgcacgttc agaagtcggt taataacgac atgatagtca 450

ctgacaacaa cggtgcagtc aagtttccac aactgtgtaa attttgtgat 500 ctgacaacaa cggtgcagtc aagtttccac aactgtgtaa attttgtgat 500

gtgagatttt ccacctgtga caaccagaaa tcctgcatga gcaactgcag 550 gtgagatttt ccacctgtga caaccagaaa tcctgcatga gcaactgcag 550

catcacctcc atctgtgaga agccacagga agtctgtgtg gctgtatgga 600 catcacctcc atctgtgaga agccacagga agtctgtgtg gctgtatgga 600

gaaagaatga cgagaacata acactagaga cagtttgcca tgaccccaag 650 gaaagaatga cgagaacata acactagaga cagtttgcca tgaccccaag 650

ctcccctacc atgactttat tctggaagat gctgcttctc caaagtgcat 700 ctcccctacc atgactttat tctggaagat gctgcttctc caaagtgcat 700

tatgaaggaa aaaaaaaagc ctggtgagac tttcttcatg tgttcctgta 750 tatgaaggaa aaaaaaaagc ctggtgagac tttcttcatg tgttcctgta 750

gctctgatga gtgcaatgac aacatcatct tctcagaaga atataacacc 800 gctctgatga gtgcaatgac aacatcatct tctcagaaga atataacacc 800

agcaatcctg acttgttgct agtcatattt caagtgacag gcatcagcct 850 agcaatcctg acttgttgct agtcatattt caagtgacag gcatcagcct 850

cctgccacca ctgggagttg ccatatctgt catcatcatc ttctactgct 900 cctgccacca ctgggagttg ccatatctgt catcatcatc ttctactgct 900

accgcgttaa ccggcagcag aagctgagtt caacctggga aaccggcaag 950 accgcgttaa ccggcagcag aagctgagtt caacctggga aaccggcaag 950

acgcggaagc tcatggagtt cagcgagcac tgtgccatca tcctggaaga 1000 acgcggaagc tcatggagtt cagcgagcac tgtgccatca tcctggaaga 1000

tgaccgctct gacatcagct ccacgtgtgc caacaacatc aaccacaaca 1050 tgaccgctct gacatcagct ccacgtgtgc caacaacatc aaccacaaca 1050

cagagctgct gcccattgag ctggacaccc tggtggggaa aggtcgcttt 1100 cagagctgct gcccattgag ctggacaccc tggtggggaa aggtcgcttt 1100

gctgaggtct ataaggccaa gctgaagcag aacacttcag agcagtttga 1150 gctgaggtct ataaggccaa gctgaagcag aacacttcag agcagtttga 1150

gacagtggca gtcaagatct ttccctatga ggagtatgcc tcttggaaga 1200 gacagtggca gtcaagatct ttccctatga ggagtatgcc tcttggaaga 1200

cagagaagga catcttctca gacatcaatc tgaagcatga gaacatactc 1250 cagagaagga catcttctca gacatcaatc tgaagcatga gaacatactc 1250

cagttcctga cggctgagga gcggaagacg gagttgggga aacaatactg 1300 cagttcctga cggctgagga gcggaagacg gagttgggga aacaatactg 1300

gctgatcacc gccttccacg ccaagggcaa cctacaggag tacctgacgc 1350 gctgatcacc gccttccacg ccaagggcaa cctacaggag tacctgacgc 1350

ggcatgtcat cagctgggag gacctgcgca agctgggcag ctccctcgcc 1400 ggcatgtcat cagctgggag gacctgcgca agctgggcag ctccctcgcc 1400

cgggggattg ctcacctcca cagtgatcac actccatgtg ggaggcccaa 1450 cgggggattg ctcacctcca cagtgatcac actccatgtg ggaggcccaa 1450

gatgcccatc gtgcacaggg acctcaagag ctccaatatc ctcgtgaaga 1500 gatgcccatc gtgcacaggg acctcaagag ctccaatatc ctcgtgaaga 1500

acgacctaac ctgctgcctg tgtgactttg ggctttccct gcgtctggac 1550 acgacctaac ctgctgcctg tgtgactttg ggctttccct gcgtctggac 1550

cctactctgt ctgtggatga cctggctaac agtgggcagg tgggaactgc 1600 aagatacatg gctccagaag tcctagaatc caggatgaat ttggagaatg 1650 ctgagtcctt caagcagacc gatgtctact ccatggctct ggtgctctgg 1700 gaaatgacat ctcgctgtaa tgcagtggga gaagtaaaag attatgagcc 1750 tccatttggt tccaaggtgc gggagcaccc ctgtgtcgaa agcatgaagg 1800 acaacgtgtt gagagatcga gggcgaccag aaattcccag cttctggctc 1850 aaccaccagg gcatccagat ggtgtgtgag acgttgactg agtgctggga 1900 ccacgaccca gaggcccgtc tcacagccca gtgtgtggca gaacgcttca 1950 gtgagctgga gcatctggac aggctctcgg ggaggagctg ctcggaggag 2000 aagattcctg aagacggctc cctaaacact accaaatagc tcttatgggg 2050 caggctgggc atgtccaaag aggctgcccc tctcaccaaa 2090 cctactctgt ctgtggatga cctggctaac agtgggcagg tgggaactgc 1600 aagatacatg gctccagaag tcctagaatc caggatgaat ttggagaatg 1650 ctgagtcctt caagcagacc gatgtctact ccatggctct ggtgctctgg 1700 ctcgctgtaa gaaatgacat tgcagtggga gaagtaaaag attatgagcc 1750 tccatttggt tccaaggtgc gggagcaccc ctgtgtcgaa agcatgaagg 1800 gagagatcga acaacgtgtt gggcgaccag aaattcccag cttctggctc 1850 aaccaccagg gcatccagat ggtgtgtgag acgttgactg agtgctggga 1900 gaggcccgtc ccacgaccca tcacagccca gtgtgtggca gaacgcttca 1950 gtgagctgga gcatctggac aggctctcgg ggaggagctg ctcggaggag 2000 aagattcctg aagacggctc cctaaacact accaaatagc tcttatgggg 2050 caggctgggc atgtccaaag aggctgcccc tctcaccaaa 2090

<210> 37 <210> 37

<211> 2629 <211> 2629

<212> ADN <212> DNA

<213> Homo sapiens <213> Homo sapiens

<400> 37 <400> 37

cagaggctgc tccccgcgtg gcccctgcac cagcagctcc tacaccggcg 500 cagaggctgc tccccgcgtg gcccctgcac cagcagctcc tacaccggcg 500

acccccgccc ggcacccgcg tccgcgccat ggccatctac aagcagtcac 750 acccccgccc ggcacccgcg tccgcgccat ggccatctac aagcagtcac 750

agcacatgac ggaggttgtg aggcgctgcc cccaccatga gcgctgctca 800 agcacatgac ggaggttgtg aggcgctgcc cccaccatga gcgctgctca 800

gatagcgatg gtctggcccc tcctcagcat cttatccgag tggaaggaaa 850 gatagcgatg gtctggcccc tcctcagcat cttatccgag tggaaggaaa 850

tttgcgtgtg gagtatttgg atgacagaaa cacttttcga catagtgtgg 900 tttgcgtgtg gagtatttgg atgacagaaa cacttttcga catagtgtgg 900

tggtgcccta tgagccgcct gaggttggct ctgactgtac caccatccac 950 tggtgcccta tgagccgcct gaggttggct ctgactgtac caccatccac 950

tacaactaca tgtgtaacag ttcctgcatg ggcggcatga accggaggcc 1000 catcctcacc atcatcacac tggaagactc cagtggtaat ctactgggac 1050 ggaacagctt tgaggtgcgt gtttgtgcct gtcctgggag agaccggcgc 1100 acagaggaag agaatctccg caagaaaggg gagcctcacc acgagctgcc 1150 cccagggagc actaagcgag cactgcccaa caacaccagc tcctctcccc 1200 agccaaagaa gaaaccactg gatggagaat atttcaccct tcagatccgt 1250 gggcgtgagc gcttcgagat gttccgagag ctgaatgagg ccttggaact 1300 caaggatgcc caggctggga aggagccagg ggggagcagg gctcactcca 1350 gccacctgaa gtccaaaaag ggtcagtcta cctcccgcca taaaaaactc 1400 atgttcaaga cagaagggcc tgactcagac tgacattctc cacttcttgt 1450 tccccactga cagcctccca cccccatctc tccctcccct gccattttgg 1500 gttttgggtc tttgaaccct tgcttgcaat aggtgtgcgt cagaagcacc 1550 caggacttcc atttgctttg tcccggggct ccactgaaca agttggcctg 1600 cactggtgtt ttgttgtggg gaggaggatg gggagtagga cataccagct 1650 tagattttaa ggtttttact gtgagggatg tttgggagat gtaagaaatg 1700 ttcttgcagt taagggttag tttacaatca gccacattct aggtaggtag 1750 gggcccactt caccgtacta accagggaag ctgtccctca tgttgaattt 1800 tctctaactt caaggcccat atctgtgaaa tgctggcatt tgcacctacc 1850 tcacagagtg cattgtgagg gttaatgaaa taatgtacat ctggccttga 1900 aaccaccttt tattacatgg ggtctaaaac ttgaccccct tgagggtgcc 1950 tgttccctct ccctctccct gttggctggt gggttggtag tttctacagt 2000 tgggcagctg gttaggtaga gggagttgtc aagtcttgct ggcccagcca 2050 aaccctgtct gacaacctct tggtcgacct tagtacctaa aaggaaatct 2100 caccccatcc cacaccctgg aggatttcat ctcttgtata tgatgatctg 2150 gatccaccaa gacttgtttt atgctcaggg tcaatttctt ttttcttttt 2200 tttttttttt tttctttttc tttgagactg ggtctcgctt tgttgcccag 2250 gctggagtgg agtggcgtga tcttggctta ctgcagcctt tgcctccccg 2300 gctcgagcag tcctgcctca gcctccggag tagctgggac cacaggttca 2350 tgccaccatg gccagccaac ttttgcatgt tttgtagaga tggggtctca 2400 cagtgttgcc caggctggtc tcaaactcct gggctcaggc gatccacctg 2450 tctcagcctc ccagagtgct gggattacaa ttgtgagcca ccacgtggag 2500 ctggaagggt caacatcttt tacattctgc aagcacatct gcattttcac 2550 cccacccttc ccctccttct ccctttttat atcccatttt tatatcgatc 2600 tcttatttta caataaaact ttgctgcca 2629 tacaactaca tgtgtaacag ttcctgcatg ggcggcatga accggaggcc 1000 catcctcacc atcatcacac tggaagactc cagtggtaat ctactgggac 1050 ggaacagctt tgaggtgcgt gtttgtgcct gtcctgggag agaccggcgc 1100 acagaggaag agaatctccg caagaaaggg gagcctcacc acgagctgcc 1150 cccagggagc actaagcgag cactgcccaa caacaccagc tcctctcccc 1200 agccaaagaa gaaaccactg gatggagaat atttcaccct tcagatccgt 1250 gggcgtgagc gcttcgagat gttccgagag ctgaatgagg ccttggaact 1300 caggctggga caaggatgcc aggagccagg ggggagcagg gctcactcca 1350 gccacctgaa gtccaaaaag ggtcagtcta cctcccgcca taaaaaactc 1400 atgttcaaga cagaagggcc tgactcagac tgacattctc cacttcttgt 1450 cagcctccca tccccactga cccccatctc tccctcccct gccattttgg 1500 gttttgggtc tttgaaccct tgcttgcaat aggtgtgcgt cagaagcacc 1550 caggacttcc atttgctttg tcccggggct ccactgaaca agttggcctg 1600 cactggtgtt ttgttgtggg gaggaggatg gggagtagga cataccagct 1650 tagattttaa ggtttttact gtgagggatg tttgggagat gtaagaaatg 1700 ttcttgcagt taagggttag tttacaatca gccacattct aggtaggtag 1750 caccgtacta gggcccactt acc agggaag ctgtccctca tgttgaattt 1800 tctctaactt caaggcccat atctgtgaaa tgctggcatt tgcacctacc 1850 tcacagagtg cattgtgagg gttaatgaaa taatgtacat ctggccttga 1900 aaccaccttt tattacatgg ggtctaaaac ttgaccccct tgagggtgcc 1950 tgttccctct ccctctccct gttggctggt gggttggtag tttctacagt 2000 tgggcagctg gttaggtaga gggagttgtc aagtcttgct ggcccagcca 2050 aaccctgtct gacaacctct tggtcgacct tagtacctaa aaggaaatct 2100 caccccatcc cacaccctgg aggatttcat ctcttgtata tgatgatctg 2150 gatccaccaa gacttgtttt atgctcaggg tcaatttctt ttttcttttt 2200 tttttttttt tttctttttc tttgagactg ggtctcgctt tgttgcccag 2250 gctggagtgg agtggcgtga tcttggctta ctgcagcctt tgcctccccg 2300 gctcgagcag tcctgcctca gcctccggag tagctgggac cacaggttca 2350 tgccaccatg gccagccaac ttttgcatgt tggggtctca tttgtagaga 2400 cagtgttgcc caggctggtc tcaaactcct gggctcaggc gatccacctg 2450 tctcagcctc ccagagtgct gggattacaa ttgtgagcca ccacgtggag 2500 ctggaagggt caacatcttt tacattctgc aagcacatct gcattttcac 2550 cccacccttc ccctccttct ccctttttat atcccatttt tatatc gatc 2600 tcttatttta caataaaact ttgctgcca 2629

<210> 38 <211> 1130 <210> 38 <211> 1130

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 38 Met Leu Glu Ile Cys Leu Lys Leu Val Gly Cys Lys Ser Lys Lys 1 5 10 15 <400> 38 Met Leu Glu Ile Cys Leu Lys Leu Val Gly Cys Lys Ser Lys Lys 1 5 10 15

Gly Leu Ser Ser Ser Ser Ser Cys Tyr Leu Glu Glu Ala Leu Gln 20 25 30 Gly Leu Be Be Be Be Be Cys Tyr Leu Glu Glu Ala Leu Gln 20 25 30

Arg Pro Val Ala Ser Asp Phe Glu Pro Gln Gly Leu Ser Glu Ala 35 40 45 Arg Pro Val Ala Ser Asp Phe Glu Pro Gln Gly Leu Ser Glu Ala 35 40 45

Ala Arg Trp Asn Ser Lys Glu Asn Leu Leu Ala Gly Pro Ser Glu 50 55 60 Wing Arg Trp Asn Ser Lys Glu Asn Leu Leu Wing Gly Pro Ser Glu 50 55 60

Asn Asp Pro Asn Leu Phe Val Ala Leu Tyr Asp Phe Val Ala Ser 65 70 75 Asn Asp Pro Asn Leu Phe Val Ala Leu Tyr Asp Phe Val Ala Ser 65 70 75

Gly Asp Asn Thr Leu Ser Ile Thr Lys Gly Glu Lys Leu Arg Val 80 85 90 Gly Asp Asn Thr Leu Ser Ile Thr Lys Gly Glu Lys Leu Arg Val 80 85 90

Leu Gly Tyr Asn His Asn Gly Glu Trp Cys Glu Ala Gln Thr Lys 95 100 105 Leu Gly Tyr Asn His Asn Gly Glu Trp Cys Glu Ala Gln Thr Lys 95 100 105

Asn Gly Gln Gly Trp Val Pro Ser Asn Tyr Ile Thr Pro Val Asn 110 115 120 Asn Gly Gln Gly Trp Val Pro Ser Asn Tyr Ile Thr Pro Val Asn 110 115 120

Ser Leu Glu Lys His Ser Trp Tyr His Gly Pro Val Ser Arg Asn 125 130 135 Ser Leu Glu Lys His Ser Trp Tyr His Gly Pro Val Ser Arg Asn 125 130 135

Ala Ala Glu Tyr Leu Leu Ser Ser Gly Ile Asn Gly Ser Phe Leu 140 145 150 Wing Wing Glu Tyr Leu Leu Ser Be Gly Ile Asn Gly Ser Phe Leu 140 145 150

Val Arg Glu Ser Glu Ser Ser Pro Gly Gln Arg Ser Ile Ser Leu 155 160 165 Val Arg Glu Ser Glu Ser Ser Pro Gly Gln Arg Ser Ile Ser Leu 155 160 165

Arg Tyr Glu Gly Arg Val Tyr His Tyr Arg Ile Asn Thr Ala Ser 170 175 180 Arg Tyr Glu Gly Arg Val Tyr His Tyr Arg Ile Asn Thr Ala Ser 170 175 180

Asp Gly Lys Leu Tyr Val Ser Ser Glu Ser Arg Phe Asn Thr Leu 185 190 195 Asp Gly Lys Leu Tyr Val Ser Ser Glu Ser Arg Phe Asn Thr Leu 185 190 195

Ala Glu Leu Val His His His Ser Thr Val Ala Asp Gly Leu Ile 200 205 210 Wing Glu Leu Val His His Ser Ser Thr Val Wing Asp Gly Leu Ile 200 205 210

Thr Thr Leu His Tyr Pro Ala Pro Lys Arg Asn Lys Pro Thr Val 215 220 225 Thr Thr Leu His Tyr Pro Ala Pro Lys Arg Asn Lys Pro Thr Val 215 220 225

Tyr Gly Val Ser Pro Asn Tyr Asp Lys Trp Glu Met Glu Arg Thr 230 235 240 Tyr Gly Val Ser Pro Asn Tyr Asp Lys Trp Glu Met Glu Arg Thr 230 235 240

Asp Ile Thr Met Lys His Lys Leu Gly Gly Gly Gln Tyr Gly Glu 245 250 255 Asp Ile Thr Met Lys His Lys Leu Gly Gly Gly Gln Tyr Gly Glu 245 250 255

Val Tyr Glu Gly Val Trp Lys Lys Tyr Ser Leu Thr Val Ala Val 260 265 270 Val Tyr Glu Gly Val Trp Lys Lys Tyr Ser Leu Thr Val Ala Val 260 265 270

Lys Thr Leu Lys Glu Asp Thr Met Glu Val Glu Glu Phe Leu Lys 275 280 285 Lys Thr Leu Lys Glu Asp Thr Met Glu Val Glu Glu Phe Leu Lys 275 280 285

Glu Ala Ala Val Met Lys Glu Ile Lys His Pro Asn Leu Val Gln 290 295 300 Glu Ala Wing Val Met Lys Glu Ile Lys His Pro Asn Leu Val Gln 290 295 300

Leu Leu Gly Val Cys Thr Arg Glu Pro Pro Phe Tyr Ile Ile Thr 305 310 315 Glu Phe Met Thr Tyr Gly Asn Leu Leu Asp Tyr Leu Arg Glu Cys 320 325 Leu Leu Gly Val Cys Thr Arg Glu Pro Pro Phe Tyr Ile Ile Thr 305 310 315 Glu Phe Met Thr Tyr Gly Asn Leu Leu Asp Tyr Leu Arg Glu Cys 320 325

Asn Arg Gln Glu Val Asn Ala Val Val Leu Leu Tyr Met Ala Thr 335 340 345 Asn Arg Gln Glu Val Asn Wing Val Val Leu Leu Tyr Met Wing Thr 335 340 345

Gln Ile Ser Ser Ala Met Glu Tyr Leu Glu Lys Lys Asn Phe Ile 350 355 360 Gln Ile Ser Ser Ala Met Glu Tyr Leu Glu Lys Lys Asn Phe Ile 350 355 360

His Arg Asp Leu Ala Ala Arg Asn Cys Leu Val Gly Glu Asn His 365 370 375 His Arg Asp Leu Ala Wing Arg Asn Cys Leu Val Gly Glu Asn His 365 370 375

Leu Val Lys Val Ala Asp Phe Gly Leu Ser Arg Leu Met Thr Gly 380 385 390 Leu Val Lys Val Wing Asp Phe Gly Leu Ser Arg Leu Met Thr Gly 380 385 390

Asp Thr Tyr Thr Ala His Ala Gly Ala Lys Phe Pro Ile Lys Trp 395 400 405 Asp Thr Tyr Thr Wing His Wing Gly Wing Lys Phe Pro Ile Lys Trp 395 400 405

Thr Ala Pro Glu Ser Leu Ala Tyr Asn Lys Phe Ser Ile Lys Ser 410 415 420 Thr Wing Pro Glu Ser Leu Wing Tyr Asn Lys Phe Ser Ile Lys Ser 410 415 420

Asp Val Trp Ala Phe Gly Val Leu Leu Trp Glu Ile Ala Thr Tyr 425 430 435 Asp Val Trp Wing Phe Gly Val Leu Leu Trp Glu Ile Wing Thr Tyr 425 430 435

Gly Met Ser Pro Tyr Pro Gly Ile Asp Leu Ser Gln Val Tyr Glu 440 445 450 Gly Met Ser Pro Tyr Pro Gly Ile Asp Leu Ser Gln Val Tyr Glu 440 445 450

Leu Leu Glu Lys Asp Tyr Arg Met Glu Arg Pro Glu Gly Cys Pro 455 460 465 Leu Leu Glu Lys Asp Tyr Arg Met Glu Arg Pro Glu Gly Cys Pro 455 460 465

Glu Lys Val Tyr Glu Leu Met Arg Ala Cys Trp Gln Trp Asn Pro 470 475 480 Glu Lys Val Tyr Glu Leu Met Arg Ala Cys Trp Gln Trp Asn Pro 470 475 480

Ser Asp Arg Pro Ser Phe Ala Glu Ile His Gln Ala Phe Glu Thr 485 490 495 Ser Asp Arg Pro Ser Phe Ala Glu Ile His Gln Ala Phe Glu Thr 485 490 495

Met Phe Gln Glu Ser Ser Ile Ser Asp Glu Val Glu Lys Glu Leu 500 505 510 Met Phe Gln Glu Ser Ser Ile Ser Asp Glu Val Glu Lys Glu Leu 500 505 510

Gly Lys Gln Gly Val Arg Gly Ala Val Ser Thr Leu Leu Gln Ala 515 520 525 Gly Lys Gln Gly Val Arg Gly Ala Val Ser Thr Leu Leu Gln Ala 515 520 525

Pro Glu Leu Pro Thr Lys Thr Arg Thr Ser Arg Arg Ala Ala Glu 530 535 540 Pro Glu Leu Pro Thr Lys Thr Arg Thr Ser Arg Arg Ala Ala Glu 530 535 540

His Arg Asp Thr Thr Asp Val Pro Glu Met Pro His Ser Lys Gly 545 550 555 His Arg Asp Thr Thr Asp Val Pro Glu Met Pro His Ser Lys Gly 545 550 555

Gln Gly Glu Ser Asp Pro Leu Asp His Glu Pro Ala Val Ser Pro 560 565 570 Gln Gly Glu Ser Asp Pro Leu Asp His Glu Pro Ala Val Ser Pro 560 565 570

Leu Leu Pro Arg Lys Glu Arg Gly Pro Pro Glu Gly Gly Leu Asn 575 580 585 Leu Leu Pro Arg Lys Glu Arg Gly Pro Pro Glu Gly Gly Leu Asn 575 580 585

Glu Asp Glu Arg Leu Leu Pro Lys Asp Lys Lys Thr Asn Leu Phe 590 595 600 Glu Asp Glu Arg Leu Leu Pro Lys Asp Lys Lys Thr Asn Leu Phe 590 595 600

Ser Ala Leu Ile Lys Lys Lys Lys Lys Thr Ala Pro Thr Pro Pro 605 610 615 Ser Ala Leu Ile Lys Lys Lys Lys Lys Thr Ala Pro Thr Pro Pro 605 610 615

Lys Arg Ser Ser Ser Phe Arg Glu Met Asp Gly Gln Pro Glu Arg 620 625 630 Lys Arg Be Be Be Phe Arg Glu Met Asp Gly Gln Pro Glu Arg 620 625 630

Arg Gly Ala Gly Glu Glu Glu Gly Arg Asp Ile Ser Asn Gly Ala 635 640 645 Arg Gly Ala Gly Glu Glu Glu Gly Arg Asp Ile Ser Asn Gly Ala 635 640 645

Leu Ala Phe Thr Pro Leu Asp Thr Ala Asp Pro Ala Lys Ser Pro 650 655 Leu Wing Phe Thr Pro Leu Asp Thr Wing Asp Pro Wing Lys Ser Pro 650 655

Lys Pro Ser Asn Gly Ala Gly Val Pro Asn Gly Ala Leu Arg Glu 665 670 Lys Pro Ser Asn Gly Ala Gly Val Pro Asn Gly Ala Leu Arg Glu 665 670

Ser Gly Gly Ser Gly Phe Arg Ser Pro His Leu Trp Lys Lys Ser 680 685 690 Ser Gly Gly Ser Gly Phe Arg Ser Pro His Leu Trp Lys Lys Ser 680 685 690

Ser Thr Leu Thr Ser Ser Arg Leu Ala Thr Gly Glu Glu Glu Gly 695 700 705 Ser Thr Leu Thr Ser Ser Arg Leu Ala Thr Gly Glu Glu Glu Gly 695 700 705

Gly Gly Ser Ser Ser Lys Arg Phe Leu Arg Ser Cys Ser Ala Ser 710 715 720 Gly Gly Ser Ser Ser Lys Arg Phe Leu Arg Ser Cys Ser Ala Ser 710 715 720

Cys Val Pro His Gly Ala Lys Asp Thr Glu Trp Arg Ser Val Thr 725 730 735 Cys Val Pro His Gly Ala Lys Asp Thr Glu Trp Arg Ser Val Thr 725 730 735

Leu Pro Arg Asp Leu Gln Ser Thr Gly Arg Gln Phe Asp Ser Ser 740 745 750 Leu Pro Arg Asp Leu Gln Ser Thr Gly Arg Gln Phe Asp Ser Ser 740 745 750

Thr Phe Gly Gly His Lys Ser Glu Lys Pro Ala Leu Pro Arg Lys 755 760 765 Thr Phe Gly Gly His Lys Ser Glu Lys Pro Ala Leu Pro Arg Lys 755 760 765

Arg Ala Gly Glu Asn Arg Ser Asp Gln Val Thr Arg Gly Thr Val 770 775 780 Arg Wing Gly Glu Asn Arg Ser Asp Gln Val Thr Arg Gly Thr Val 770 775 780

Thr Pro Pro Pro Arg Leu Val Lys Lys Asn Glu Glu Ala Ala Asp 785 790 795 Thr Pro Pro Pro Arg Leu Val Lys Lys Asn Glu Glu Ala Wing Asp 785 790 795

Glu Val Phe Lys Asp Ile Met Glu Ser Ser Pro Gly Ser Ser Pro 800 805 810 Glu Val Phe Lys Asp Ile Met Glu Ser Ser Pro Gly Ser Ser Pro 800 805 810

Pro Asn Leu Thr Pro Lys Pro Leu Arg Arg Gln Val Thr Val Ala 815 820 825 Pro Asn Leu Thr Pro Lys Pro Leu Arg Arg Gln Val Thr Val Wing 815 820 825

Pro Ala Ser Gly Leu Pro His Lys Glu Glu Ala Gly Lys Gly Ser 830 835 840 Pro Wing Ser Gly Leu Pro His Lys Glu Glu Wing Gly Lys Gly Ser 830 835 840

Ala Leu Gly Thr Pro Ala Ala Ala Glu Pro Val Thr Pro Thr Ser 845 850 855 Wing Leu Gly Thr Pro Wing Wing Glu Pro Val Thr Pro Thr Ser 845 850 855

Lys Ala Gly Ser Gly Ala Pro Gly Gly Thr Ser Lys Gly Pro Ala 860 865 870 Lys Wing Gly Ser Gly Wing Pro Gly Gly Thr Ser Lys Gly Pro Wing 860 865 870

Glu Glu Ser Arg Val Arg Arg His Lys His Ser Ser Glu Ser Pro 875 880 885 Glu Glu Ser Arg Val Arg Arg His Lys His Ser Ser Glu Ser Pro 875 880 885

Gly Arg Asp Lys Gly Lys Leu Ser Arg Leu Lys Pro Ala Pro Pro 890 895 900 Gly Arg Asp Lys Gly Lys Leu Ser Arg Leu Lys Pro Wing Pro Pro 890 895 900

Pro Pro Pro Ala Ala Ser Ala Gly Lys Ala Gly Gly Lys Pro Ser 905 910 915 Pro Pro Pro Wing Wing Be Wing Gly Lys Wing Gly Gly Lys Pro Ser 905 910 915

Gln Ser Pro Ser Gln Glu Ala Ala Gly Glu Ala Val Leu Gly Ala 920 925 930 Gln Ser Pro Ser Gln Glu Ala Wing Gly Glu Ala Val Leu Gly Ala 920 925 930

Lys Thr Lys Ala Thr Ser Leu Val Asp Ala Val Asn Ser Asp Ala 935 940 945 Lys Thr Lys Ala Thr Ser Leu Val Asp Ala Val Asn Ser Asp Ala 935 940 945

Ala Lys Pro Ser Gln Pro Gly Glu Gly Leu Lys Lys Pro Val Leu 950 955 960 Wing Lys Pro Ser Gln Pro Gly Glu Gly Leu Lys Lys Pro Val Leu 950 955 960

Pro Ala Thr Pro Lys Pro Gln Ser Ala Lys Pro Ser Gly Thr Pro 965 970 975 Pro Wing Thr Pro Lys Pro Gln Ser Wing Lys Pro Ser Gly Thr Pro 965 970 975

Ile Ser Pro Ala Pro Val Pro Ser Thr Leu Pro Ser Ala Ser Ser 980 985 990 Ile Ser Pro Ala Pro Val Pro Ser Thr Leu Pro Ser Ala Ser Ser 980 985 990

Ala Leu Ala Gly Asp Gln Pro Ser Ser Thr Ala Phe Ile Pro Leu Wing Leu Wing Gly Asp Gln Pro Ser Ser Thr Wing Phe Ile Pro Leu

995 1000 1005 995 1000 1005

Ile Ser Thr Arg Val Ser Leu Arg Lys Thr Arg Gln Pro Pro Glu 1010 1015 1020 Ile Ser Thr Arg Val Ser Leu Arg Lys Thr Arg Gln Pro Pro Glu 1010 1015 1020

Arg Ile Ala Ser Gly Ala Ile Thr Lys Gly Val Val Leu Asp Ser 1025 1030 1035 Arg Ile Wing Ser Gly Wing Ile Thr Lys Gly Val Val Leu Asp Ser 1025 1030 1035

Thr Glu Ala Leu Cys Leu Ala Ile Ser Arg Asn Ser Glu Gln Met 1040 1045 1050 Thr Glu Ala Leu Cys Leu Ala Ile Ser Arg Asn Ser Glu Gln Met 1040 1045 1050

Ala Ser His Ser Ala Val Leu Glu Ala Gly Lys Asn Leu Tyr Thr 1055 1060 1065 Ala Ser His Ser Ala Val Leu Glu Ala Gly Lys Asn Leu Tyr Thr 1055 1060 1065

Phe Cys Val Ser Tyr Val Asp Ser Ile Gln Gln Met Arg Asn Lys 1070 1075 1080 Phe Cys Val Ser Tyr Val Asp Ser Ile Gln Gln Met Arg Asn Lys 1070 1075 1080

Phe Ala Phe Arg Glu Ala Ile Asn Lys Leu Glu Asn Asn Leu Arg 1085 1090 1095 Phe Ala Phe Arg Glu Ile Wing Asn Lys Leu Glu Asn Asn Leu Arg 1085 1090 1095

Glu Leu Gln Ile Cys Pro Ala Thr Ala Gly Ser Gly Pro Ala Ala 1100 1105 1110 Glu Leu Gln Ile Cys Pro Wing Thr Wing Gly Ser Gly Pro Wing Wing 1100 1105 1110

Thr Gln Asp Phe Ser Lys Leu Leu Ser Ser Val Lys Glu Ile Ser 1115 1120 1125 Thr Gln Asp Phe Ser Lys Leu Leu Ser Ser Val Lys Glu Ile Ser 1115 1120 1125

Asp Ile Val Gln Arg 1130 Asp Ile Val Gln Arg 1130

<210> 39 <210> 39

<211> 2843 <211> 2843

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 39 Met Ala Ala Ala Ser Tyr Asp Gln Leu Leu Lys Gln Val Glu Ala 1 5 10 15 <400> 39 Met Wing Wing Be Ser Tyr Asp Gln Leu Leu Lys Gln Val Glu Ala 1 5 10 15

Leu Lys Met Glu Asn Ser Asn Leu Arg Gln Glu Leu Glu Asp Asn 20 25 30 Leu Lys Met Glu Asn Ser Asn Leu Arg Gln Glu Leu Glu Asp Asn 20 25 30

Ser Asn His Leu Thr Lys Leu Glu Thr Glu Ala Ser Asn Met Lys 35 40 45 Be Asn His Leu Thr Lys Leu Glu Thr Glu Ala Be Asn Met Lys 35 40 45

Glu Val Leu Lys Gln Leu Gln Gly Ser Ile Glu Asp Glu Ala Met 50 55 60 Glu Val Leu Lys Gln Leu Gln Gly Ser Ile Glu Asp Glu Ala Met 50 55 60

Ala Ser Ser Gly Gln Ile Asp Leu Leu Glu Arg Leu Lys Glu Leu 65 70 75 Wing Be Being Gly Gln Ile Asp Leu Leu Glu Arg Leu Lys Glu Leu 65 70 75

Asn Leu Asp Ser Ser Asn Phe Pro Gly Val Lys Leu Arg Ser Lys 80 85 90 Asn Leu Asp Ser Be Asn Phe Pro Gly Val Lys Leu Arg Ser Lys 80 85 90

Met Ser Leu Arg Ser Tyr Gly Ser Arg Glu Gly Ser Val Ser Ser 95 100 105 Met Ser Leu Arg Ser Tyr Gly Ser Arg Glu Gly Ser Val Ser Ser 95 100 105

Arg Ser Gly Glu Cys Ser Pro Val Pro Met Gly Ser Phe Pro Arg 110 115 120 Arg Ser Gly Glu Cys Ser Pro Val Pro Met Gly Ser Phe Pro Arg 110 115 120

Arg Gly Phe Val Asn Gly Ser Arg Glu Ser Thr Gly Tyr Leu Glu 125 130 135 Arg Gly Phe Val Asn Gly Ser Arg Glu Ser Thr Gly Tyr Leu Glu 125 130 135

Glu Leu Glu Lys Glu Arg Ser Leu Leu Leu Ala Asp Leu Asp Lys 140 145 150 Glu Leu Glu Lys Glu Arg Ser Leu Leu Leu Wing Asp Leu Asp Lys 140 145 150

Glu Glu Lys Glu Lys Asp Trp Tyr Tyr Ala Gln Leu Gln Asn Leu 155 160 165 Thr Lys Arg Ile Asp Ser Leu Pro Leu Thr Glu Asn Phe Ser Leu 170 175 Glu Glu Lys Glu Lys Asp Trp Tyr Tyr Wing Gln Leu Gln Asn Leu 155 160 165 Thr Lys Arg Ile Asp Ser Leu Pro Leu Thr Glu Asn Phe Ser Leu 170 175

Gln Thr Asp Met Thr Arg Arg Gln Leu Glu Tyr Glu Ala Arg Gln 185 190 195 Gln Thr Asp Met Thr Arg Arg Gln Leu Glu Tyr Glu Ala Arg Gln 185 190 195

Ile Arg Val Ala Met Glu Glu Gln Leu Gly Thr Cys Gln Asp Met 200 205 210 Ile Arg Val Wing Met Glu Glu Gln Leu Gly Thr Cys Gln Asp Met 200 205 210

Glu Lys Arg Ala Gln Arg Arg Ile Ala Arg Ile Gln Gln Ile Glu 215 220 225 Glu Lys Arg Wing Gln Arg Arg Ile Wing Arg Ile Gln Gln Ile Glu 215 220 225

Lys Asp Ile Leu Arg Ile Arg Gln Leu Leu Gln Ser Gln Ala Thr 230 235 240 Lys Asp Ile Leu Arg Ile Arg Gln Leu Leu Gln Ser Gln Ala Thr 230 235 240

Glu Ala Glu Arg Ser Ser Gln Asn Lys His Glu Thr Gly Ser His 245 250 255 Glu Ala Glu Arg Ser Ser Gln Asn Lys His Glu Thr Gly Ser His 245 250 255

Asp Ala Glu Arg Gln Asn Glu Gly Gln Gly Val Gly Glu Ile Asn 260 265 270 Asp Wing Glu Arg Gln Asn Glu Gly Gln Gly Val Gly Glu Ile Asn 260 265 270

Met Ala Thr Ser Gly Asn Gly Gln Gly Ser Thr Thr Arg Met Asp 275 280 285 Met Wing Thr Ser Gly Asn Gly Gln Gly Ser Thr Thr Arg Met Asp 275 280 285

His Glu Thr Ala Ser Val Leu Ser Ser Ser Ser Thr His Ser Ala 290 295 300 His Glu Thr Ala Ser Val Leu Ser Ser Ser Ser Thr His Ser Ala 290 295 300

Pro Arg Arg Leu Thr Ser His Leu Gly Thr Lys Val Glu Met Val 305 310 315 Pro Arg Arg Leu Thr Ser His Leu Gly Thr Lys Val Glu Met Val 305 310 315

Tyr Ser Leu Leu Ser Met Leu Gly Thr His Asp Lys Asp Asp Met 320 325 330 Tyr Ser Leu Leu Ser Met Leu Gly Thr His Asp Lys Asp Asp Met 320 325 330

Ser Arg Thr Leu Leu Ala Met Ser Ser Ser Gln Asp Ser Cys Ile 335 340 345 Be Arg Thr Leu Leu Wing Met Be Be Be Gln Asp Be Cys Ile 335 340 345

Ser Met Arg Gln Ser Gly Cys Leu Pro Leu Leu Ile Gln Leu Leu 350 355 360 Ser Met Arg Gln Ser Gly Cys Leu Pro Leu Leu Ile Gln Leu Leu 350 355 360

His Gly Asn Asp Lys Asp Ser Val Leu Leu Gly Asn Ser Arg Gly 365 370 375 His Gly Asn Asp Lys Asp Ser Val Leu Leu Gly Asn Ser Arg Gly 365 370 375

Ser Lys Glu Ala Arg Ala Arg Ala Ser Ala Ala Leu His Asn Ile 380 385 390 Ser Lys Glu Ala Arg Ala Arg Ala Ser Ala Ala Leu His Asn Ile 380 385 390

Ile His Ser Gln Pro Asp Asp Lys Arg Gly Arg Arg Glu Ile Arg 395 400 405 Ile His Ser Gln Pro Asp Asp Lys Arg Gly Arg Arg Glu Ile Arg 395 400 405

Val Leu His Leu Leu Glu Gln Ile Arg Ala Tyr Cys Glu Thr Cys 410 415 420 Val Leu His Leu Leu Glu Gln Ile Arg Ala Tyr Cys Glu Thr Cys 410 415 420

Trp Glu Trp Gln Glu Ala His Glu Pro Gly Met Asp Gln Asp Lys 425 430 435 Trp Glu Trp Gln Glu Ala His Glu Pro Gly Met Asp Gln Asp Lys 425 430 435

Asn Pro Met Pro Ala Pro Val Glu His Gln Ile Cys Pro Ala Val 440 445 450 Asn Pro Met Pro Wing Pro Val Glu His Gln Ile Cys Pro Wing Val 440 445 450

Cys Val Leu Met Lys Leu Ser Phe Asp Glu Glu His Arg His Ala 455 460 465 Cys Val Leu Met Lys Leu Ser Phe Asp Glu Glu His Arg His Ala 455 460 465

Met Asn Glu Leu Gly Gly Leu Gln Ala Ile Ala Glu Leu Leu Gln 470 475 480 Met Asn Glu Leu Gly Gly Leu Gln Ile Wing Glu Leu Leu Gln 470 475 480

Val Asp Cys Glu Met Tyr Gly Leu Thr Asn Asp His Tyr Ser Ile 485 490 495 Val Asp Cys Glu Met Tyr Gly Leu Thr Asn Asp His Tyr Ser Ile 485 490 495

Thr Leu Arg Arg Tyr Ala Gly Met Ala Leu Thr Asn Leu Thr Phe 500 505 Thr Leu Arg Arg Tyr Ala Gly Met Ala Leu Thr Asn Leu Thr Phe 500 505

Gly Asp Val Ala Asn Lys Ala Thr Leu Cys Ser Met Lys Gly Cys 515 520 Gly Asp Val Wing Asn Lys Wing Thr Leu Cys Ser Met Lys Gly Cys 515 520

Met Arg Ala Leu Val Ala Gln Leu Lys Ser Glu Ser Glu Asp Leu 530 535 540 Met Arg Ala Leu Val Ala Gln Leu Lys Ser Glu Ser Glu Asp Leu 530 535 540

Gln Gln Val Ile Ala Ser Val Leu Arg Asn Leu Ser Trp Arg Ala 545 550 555 Gln Gln Val Ile Wing Ser Val Leu Arg Asn Leu Ser Trp Arg Wing 545 550 555

Asp Val Asn Ser Lys Lys Thr Leu Arg Glu Val Gly Ser Val Lys 560 565 570 Asp Val Asn Ser Lys Lys Thr Leu Arg Glu Val Gly Ser Val Lys 560 565 570

Ala Leu Met Glu Cys Ala Leu Glu Val Lys Lys Glu Ser Thr Leu 575 580 585 Wing Leu Met Glu Cys Wing Leu Glu Val Lys Lys Glu Ser Thr Leu 575 580 585

Lys Ser Val Leu Ser Ala Leu Trp Asn Leu Ser Ala His Cys Thr 590 595 600 Lys Ser Val Leu Ser Ala Leu Trp Asn Leu Ser Ala His Cys Thr 590 595 600

Glu Asn Lys Ala Asp Ile Cys Ala Val Asp Gly Ala Leu Ala Phe 605 610 615 Glu Asn Lys Wing Asp Ile Cys Wing Val Asp Gly Wing Leu Wing Phe 605 610 615

Leu Val Gly Thr Leu Thr Tyr Arg Ser Gln Thr Asn Thr Leu Ala 620 625 630 Leu Val Gly Thr Leu Thr Tyr Arg Ser Gln Thr Asn Thr Leu Wing 620 625 630

Ile Ile Glu Ser Gly Gly Gly Ile Leu Arg Asn Val Ser Ser Leu 635 640 645 Ile Ile Glu Ser Gly Gly Gly Ile Leu Arg Asn Val Ser Ser Leu 635 640 645

Ile Ala Thr Asn Glu Asp His Arg Gln Ile Leu Arg Glu Asn Asn 650 655 660 Ile Ala Thr Asn Glu Asp His Arg Gln Ile Leu Arg Glu Asn Asn 650 655 660

Cys Leu Gln Thr Leu Leu Gln His Leu Lys Ser His Ser Leu Thr 665 670 675 Cys Leu Gln Thr Leu Leu Gln His Leu Lys Ser His Ser Leu Thr 665 670 675

Ile Val Ser Asn Ala Cys Gly Thr Leu Trp Asn Leu Ser Ala Arg 680 685 690 Ile Val Ser Asn Ala Cys Gly Thr Leu Trp Asn Leu Ser Ala Arg 680 685 690

Asn Pro Lys Asp Gln Glu Ala Leu Trp Asp Met Gly Ala Val Ser 695 700 705 Asn Pro Lys Asp Gln Glu Ala Leu Trp Asp Met Gly Ala Val Ser 695 700 705

Met Leu Lys Asn Leu Ile His Ser Lys His Lys Met Ile Ala Met 710 715 720 Met Leu Lys Asn Leu Ile His Ser Lys His Lys Met Ile Wing Met 710 715 720

Gly Ser Ala Ala Ala Leu Arg Asn Leu Met Ala Asn Arg Pro Ala 725 730 735 Gly Ser Wing Wing Leu Arg Asn Leu Met Wing Asn Arg Pro Wing 725 730 735

Lys Tyr Lys Asp Ala Asn Ile Met Ser Pro Gly Ser Ser Leu Pro 740 745 750 Lys Tyr Lys Asp Wing Asn Ile Met Ser Pro Gly Ser Ser Leu Pro 740 745 750

Ser Leu His Val Arg Lys Gln Lys Ala Leu Glu Ala Glu Leu Asp 755 760 765 Ser Leu His Val Arg Lys Gln Lys Ala Leu Glu Ala Glu Leu Asp 755 760 765

Ala Gln His Leu Ser Glu Thr Phe Asp Asn Ile Asp Asn Leu Ser 770 775 780 Gln Wing His Leu Ser Glu Thr Phe Asp Asn Ile Asp Asn Leu Ser 770 775 780

Pro Lys Ala Ser His Arg Ser Lys Gln Arg His Lys Gln Ser Leu 785 790 795 Pro Lys Ala Ser His Arg Ser Lys Gln Arg His Lys Gln Ser Leu 785 790 795

Tyr Gly Asp Tyr Val Phe Asp Thr Asn Arg His Asp Asp Asn Arg 800 805 810 Tyr Gly Asp Tyr Val Phe Asp Thr Asn Arg His Asp Asp Asn Arg 800 805 810

Ser Asp Asn Phe Asn Thr Gly Asn Met Thr Val Leu Ser Pro Tyr 815 820 825 Ser Asp Asn Phe Asn Thr Gly Asn Met Thr Val Leu Ser Pro Tyr 815 820 825

Leu Asn Thr Thr Val Leu Pro Ser Ser Ser Ser Ser Arg Gly Ser 830 835 840 Leu Asn Thr Thr Val Leu Pro Be Be Be Be Be Arg Gly Ser 830 835 840

Leu Asp Ser Ser Arg Ser Glu Lys Asp Arg Ser Leu Glu Arg Glu Leu Asp Be Ser Arg Be Glu Lys Asp Arg Be Leu Glu Arg Glu

845 850 845 850

Arg Gly Ile Gly Leu Gly Asn Tyr His Pro Ala Thr Glu Asn Pro 860 865 870 Arg Gly Ile Gly Leu Gly Asn Tyr His Pro Wing Thr Glu Asn Pro 860 865 870

Gly Thr Ser Ser Lys Arg Gly Leu Gln Ile Ser Thr Thr Ala Ala 875 880 885 Gly Thr Ser Ser Lys Arg Gly Leu Gln Ile Ser Thr Thr Ala Wing 875 880 885

Gln Ile Ala Lys Val Met Glu Glu Val Ser Ala Ile His Thr Ser 890 895 900 Gln Ile Wing Lys Val Met Glu Glu Val Ser Wing Ile His Thr Ser 890 895 900

Gln Glu Asp Arg Ser Ser Gly Ser Thr Thr Glu Leu His Cys Val 905 910 915 Gln Glu Asp Arg Ser Ser Gly Ser Thr Thr Glu Leu His Cys Val 905 910 915

Thr Asp Glu Arg Asn Ala Leu Arg Arg Ser Ser Ala Ala His Thr 920 925 930 Thr Asp Glu Arg Asn Ala Leu Arg Arg Ser Ser Ala Ala His Thr 920 925 930

His Ser Asn Thr Tyr Asn Phe Thr Lys Ser Glu Asn Ser Asn Arg 935 940 945 His Ser Asn Thr Tyr Asn Phe Thr Lys Ser Glu Asn Ser Asn Arg 935 940 945

Thr Cys Ser Met Pro Tyr Ala Lys Leu Glu Tyr Lys Arg Ser Ser 950 955 960 Thr Cys Ser Met Pro Tyr Ala Lys Leu Glu Tyr Lys Arg Ser Ser 950 955 960

Asn Asp Ser Leu Asn Ser Val Ser Ser Ser Asp Gly Tyr Gly Lys 965 970 975 Asn Asp Be Leu Asn Be Val Be Be Be Asp Gly Tyr Gly Lys 965 970 975

Arg Gly Gln Met Lys Pro Ser Ile Glu Ser Tyr Ser Glu Asp Asp 980 985 990 Arg Gly Gln Met Lys Pro Ser Ile Glu Ser Tyr Ser Glu Asp Asp 980 985 990

Glu Ser Lys Phe Cys Ser Tyr Gly Gln Tyr Pro Ala Asp Leu Ala 995 1000 1005 Glu Ser Lys Phe Cys Ser Tyr Gly Gln Tyr Pro Wing Asp Leu Wing 995 1000 1005

His Lys Ile His Ser Ala Asn His Met Asp Asp Asn Asp Gly Glu 1010 1015 1020 His Lys Ile His Ser Ala Asn His Met Asp Asp Asn Asp Gly Glu 1010 1015 1020

Leu Asp Thr Pro Ile Asn Tyr Ser Leu Lys Tyr Ser Asp Glu Gln 1025 1030 1035 Leu Asp Thr Pro Ile Asn Tyr Ser Leu Lys Tyr Ser Asp Glu Gln 1025 1030 1035

Leu Asn Ser Gly Arg Gln Ser Pro Ser Gln Asn Glu Arg Trp Ala 1040 1045 1050 Leu Asn Ser Gly Arg Gln Ser Pro Ser Gln Asn Glu Arg Trp Wing 1040 1045 1050

Arg Pro Lys His Ile Ile Glu Asp Glu Ile Lys Gln Ser Glu Gln 1055 1060 1065 Arg Pro Lys His Ile Ile Glu Asp Glu Ile Lys Gln Ser Glu Gln 1055 1060 1065

Arg Gln Ser Arg Asn Gln Ser Thr Thr Tyr Pro Val Tyr Thr Glu 1070 1075 1080 Arg Gln Ser Arg Asn Gln Ser Thr Thr Tyr Pro Val Tyr Thr Glu 1070 1075 1080

Ser Thr Asp Asp Lys His Leu Lys Phe Gln Pro His Phe Gly Gln 1085 1090 1095 Ser Thr Asp Asp Lys His Leu Lys Phe Gln Pro His Phe Gly Gln 1085 1090 1095

Gln Glu Cys Val Ser Pro Tyr Arg Ser Arg Gly Ala Asn Gly Ser 1100 1105 1110 Gln Glu Cys Val Ser Pro Tyr Arg Ser Arg Gly Ala Asn Gly Ser 1100 1105 1110

Glu Thr Asn Arg Val Gly Ser Asn His Gly Ile Asn Gln Asn Val 1115 1120 1125 Glu Thr Asn Arg Val Gly Ser Asn His Gly Ile Asn Gln Asn Val 1115 1120 1125

Ser Gln Ser Leu Cys Gln Glu Asp Asp Tyr Glu Asp Asp Lys Pro 1130 1135 1140 Ser Gln Ser Leu Cys Gln Glu Asp Asp Tyr Glu Asp Asp Lys Pro 1130 1135 1140

Thr Asn Tyr Ser Glu Arg Tyr Ser Glu Glu Glu Gln His Glu Glu 1145 1150 1155 Thr Asn Tyr Ser Glu Arg Tyr Ser Glu Glu Glu Gln His Glu Glu 1145 1150 1155

Glu Glu Arg Pro Thr Asn Tyr Ser Ile Lys Tyr Asn Glu Glu Lys 1160 1165 1170 Glu Glu Arg Pro Thr Asn Tyr Ser Ile Lys Tyr Asn Glu Glu Lys 1160 1165 1170

Arg His Val Asp Gln Pro Ile Asp Tyr Ser Leu Lys Tyr Ala Thr 1175 1180 1185 Asp Ile Pro Ser Ser Gln Lys Gln Ser Phe Ser Phe Ser Lys Ser 1190 1195 1200 Arg His Val Asp Gln Pro Ile Asp Tyr Ser Leu Lys Tyr Ala Thr 1175 1180 1185 Asp Ile Pro Be Ser Gln Lys Gln Ser Phe Ser Phe Ser Lys Ser 1190 1195 1200

Ser Ser Gly Gln Ser Ser Lys Thr Glu His Met Ser Ser Ser Ser 1205 1210 1215 Be Be Gly Gln Be Be Lys Thr Glu His Met Be Be Be Be 1205 1210 1215

Glu Asn Thr Ser Thr Pro Ser Ser Asn Ala Lys Arg Gln Asn Gln 1220 1225 1230 Glu Asn Thr Ser Thr Pro Ser Ser Asn Ala Lys Arg Gln Asn Gln 1220 1225 1230

Leu His Pro Ser Ser Ala Gln Ser Arg Ser Gly Gln Pro Gln Lys 1235 1240 1245 Leu His Pro Be Ser Wing Gln Be Arg Be Gly Gln Pro Gln Lys 1235 1240 1245

Ala Ala Thr Cys Lys Val Ser Ser Ile Asn Gln Glu Thr Ile Gln 1250 1255 1260 Wing Wing Thr Cys Lys Val Ser Ser Ile Asn Gln Glu Thr Ile Gln 1250 1255 1260

Thr Tyr Cys Val Glu Asp Thr Pro Ile Cys Phe Ser Arg Cys Ser 1265 1270 1275 Thr Tyr Cys Val Glu Asp Thr Pro Ile Cys Phe Ser Arg Cys Ser 1265 1270 1275

Ser Leu Ser Ser Leu Ser Ser Ala Glu Asp Glu Ile Gly Cys Asn 1280 1285 1290 Be Leu Be Be Leu Be Be Ala Glu Asp Glu Ile Gly Cys Asn 1280 1285 1290

Gln Thr Thr Gln Glu Ala Asp Ser Ala Asn Thr Leu Gln Ile Ala 1295 1300 1305 Gln Thr Thr Gln Glu Wing Asp Ser Wing Asn Thr Leu Gln Ile Wing 1295 1300 1305

Glu Ile Lys Glu Lys Ile Gly Thr Arg Ser Ala Glu Asp Pro Val 1310 1315 1320 Glu Ile Lys Glu Lys Ile Gly Thr Arg Ser Ala Glu Asp Pro Val 1310 1315 1320

Ser Glu Val Pro Ala Val Ser Gln His Pro Arg Thr Lys Ser Ser 1325 1330 1335 Ser Glu Val Pro Ala Val Ser Gln His Pro Arg Thr Lys Ser Ser 1325 1330 1335

Arg Leu Gln Gly Ser Ser Leu Ser Ser Glu Ser Ala Arg His Lys 1340 1345 1350 Arg Leu Gln Gly Be Be Leu Be Be Glu Be Ala Arg His Lys 1340 1345 1350

Ala Val Glu Phe Ser Ser Gly Ala Lys Ser Pro Ser Lys Ser Gly 1355 1360 1365 Ala Val Glu Phe Ser Be Gly Ala Lys Ser Pro Ser Lys Ser Gly 1355 1360 1365

Ala Gln Thr Pro Lys Ser Pro Pro Glu His Tyr Val Gln Glu Thr 1370 1375 1380 Wing Gln Thr Pro Lys Ser Pro Pro Glu His Tyr Val Gln Glu Thr 1370 1375 1380

Pro Leu Met Phe Ser Arg Cys Thr Ser Val Ser Ser Leu Asp Ser 1385 1390 1395 Pro Leu Met Phe Ser Arg Cys Thr Ser Val Ser Ser Leu Asp Ser 1385 1390 1395

Phe Glu Ser Arg Ser Ile Ala Ser Ser Val Gln Ser Glu Pro Cys 1400 1405 1410 Phe Glu Ser Arg Be Ile Ala Be Ser Val Gln Ser Glu Pro Cys 1400 1405 1410

Ser Gly Met Val Ser Gly Ile Ile Ser Pro Ser Asp Leu Pro Asp 1415 1420 1425 Be Gly Met Val Be Gly Ile Ile Ser Pro Be Asp Leu Pro Asp 1415 1420 1425

Ser Pro Gly Gln Thr Met Pro Pro Ser Arg Ser Lys Thr Pro Pro 1430 1435 1440 Ser Pro Gly Gln Thr Met Pro Pro Ser Arg Ser Lys Thr Pro Pro 1430 1435 1440

Pro Pro Pro Gln Thr Ala Gln Thr Lys Arg Glu Val Pro Lys Asn 1445 1450 1455 Pro Pro Pro Gln Thr Wing Gln Thr Lys Arg Glu Val Pro Lys Asn 1445 1450 1455

Lys Ala Pro Thr Ala Glu Lys Arg Glu Ser Gly Pro Lys Gln Ala 1460 1465 1470 Lys Wing Pro Thr Wing Glu Lys Arg Glu Ser Gly Pro Lys Gln Wing 1460 1465 1470

Ala Val Asn Ala Ala Val Gln Arg Val Gln Val Leu Pro Asp Ala 1475 1480 1485 Wing Val Asn Wing Wing Val Gln Arg Val Gln Val Leu Pro Asp Wing 1475 1480 1485

Asp Thr Leu Leu His Phe Ala Thr Glu Ser Thr Pro Asp Gly Phe 1490 1495 1500 Asp Thr Leu Leu His Phe Ala Thr Glu Ser Thr Pro Asp Gly Phe 1490 1495 1500

Ser Cys Ser Ser Ser Leu Ser Ala Leu Ser Leu Asp Glu Pro Phe 1505 1510 1515 Be Cys Be Be Be Leu Be Ala Leu Be Leu Asp Glu Pro Phe 1505 1510 1515

Ile Gln Lys Asp Val Glu Leu Arg Ile Met Pro Pro Val Gln Glu 1520 1525 1530 Asn Asp Asn Gly Asn Glu Thr Glu Ser Glu Gln Pro Lys Glu Ser 1535 1540 1545 Ile Gln Lys Asp Val Glu Leu Arg Ile Met Pro Pro Val Gln Glu 1520 1525 1530 Asn Asp Asn Gly Asn Glu Thr Glu Ser Glu Gln Pro Lys Glu Ser 1535 1540 1545

Asn Glu Asn Gln Glu Lys Glu Ala Glu Lys Thr Ile Asp Ser Glu 1550 1555 1560 Asn Glu Asn Gln Glu Lys Glu Ala Glu Lys Thr Ile Asp Ser Glu 1550 1555 1560

Lys Asp Leu Leu Asp Asp Ser Asp Asp Asp Asp Ile Glu Ile Leu 1565 1570 1575 Lys Asp Leu Leu Asp Asp Ser Asp Asp Asp Asp Ile Glu Ile Leu 1565 1570 1575

Glu Glu Cys Ile Ile Ser Ala Met Pro Thr Lys Ser Ser Arg Lys 1580 1585 1590 Glu Glu Cys Ile Ile Ser Ala Met Pro Thr Lys Ser Ser Arg Lys 1580 1585 1590

Ala Lys Lys Pro Ala Gln Thr Ala Ser Lys Leu Pro Pro Pro Val 1595 1600 1605 Wing Lys Lys Pro Wing Gln Thr Wing Ser Lys Leu Pro Pro Val Val 1595 1600 1605

Ala Arg Lys Pro Ser Gln Leu Pro Val Tyr Lys Leu Leu Pro Ser 1610 1615 1620 Wing Arg Lys Pro Ser Gln Leu Pro Val Tyr Lys Leu Leu Pro Ser 1610 1615 1620

Gln Asn Arg Leu Gln Pro Gln Lys His Val Ser Phe Thr Pro Gly 1625 1630 1635 Gln Asn Arg Leu Gln Pro Gln Lys His Val Ser Phe Thr Pro Gly 1625 1630 1635

Asp Asp Met Pro Arg Val Tyr Cys Val Glu Gly Thr Pro Ile Asn 1640 1645 1650 Asp Asp Met Pro Arg Val Tyr Cys Val Glu Gly Thr Pro Ile Asn 1640 1645 1650

Phe Ser Thr Ala Thr Ser Leu Ser Asp Leu Thr Ile Glu Ser Pro 1655 1660 1665 Phe Ser Thr Ala Thr Ser Leu Ser Asp Leu Thr Ile Glu Ser Pro 1655 1660 1665

Pro Asn Glu Leu Ala Ala Gly Glu Gly Val Arg Gly Gly Ala Gln 1670 1675 1680 Pro Asn Glu Leu Wing Wing Gly Glu Gly Val Arg Gly Gly Wing Gln 1670 1675 1680

Ser Gly Glu Phe Glu Lys Arg Asp Thr Ile Pro Thr Glu Gly Arg 1685 1690 1695 Ser Gly Glu Phe Glu Lys Arg Asp Thr Ile Pro Thr Glu Gly Arg 1685 1690 1695

Ser Thr Asp Glu Ala Gln Gly Gly Lys Thr Ser Ser Val Thr Ile 1700 1705 1710 Ser Thr Asp Glu Ala Gln Gly Gly Lys Thr Ser Ser Val Thr Ile 1700 1705 1710

Pro Glu Leu Asp Asp Asn Lys Ala Glu Glu Gly Asp Ile Leu Ala 1715 1720 1725 Pro Glu Leu Asp Asp Asn Lys Ala Glu Glu Gly Asp Ile Leu Ala 1715 1720 1725

Glu Cys Ile Asn Ser Ala Met Pro Lys Gly Lys Ser His Lys Pro 1730 1735 1740 Glu Cys Ile Asn Ser Ala Met Pro Lys Gly Lys Ser His Lys Pro 1730 1735 1740

Phe Arg Val Lys Lys Ile Met Asp Gln Val Gln Gln Ala Ser Ala 1745 1750 1755 Phe Arg Val Lys Lys Ile Met Asp Gln Val Gln Gln Ala Ser Ala 1745 1750 1755

Ser Ser Ser Ala Pro Asn Lys Asn Gln Leu Asp Gly Lys Lys Lys 1760 1765 1770 Be Be Be Wing Pro Asn Lys Asn Gln Leu Asp Gly Lys Lys Lys 1760 1765 1770

Lys Pro Thr Ser Pro Val Lys Pro Ile Pro Gln Asn Thr Glu Tyr 1775 1780 1785 Lys Pro Thr Ser Pro Val Lys Pro Ile Pro Gln Asn Thr Glu Tyr 1775 1780 1785

Arg Thr Arg Val Arg Lys Asn Ala Asp Ser Lys Asn Asn Leu Asn 1790 1795 1800 Arg Thr Arg Val Arg Lys Asn Wing Asp Ser Lys Asn Asn Leu Asn 1790 1795 1800

Ala Glu Arg Val Phe Ser Asp Asn Lys Asp Ser Lys Lys Gln Asn 1805 1810 1815 Wing Glu Arg Val Phe Ser Asp Asn Lys Asp Ser Lys Lys Gln Asn 1805 1810 1815

Leu Lys Asn Asn Ser Lys Val Phe Asn Asp Lys Leu Pro Asn Asn 1820 1825 1830 Leu Lys Asn Asn Ser Lys Val Phe Asn Asp Lys Leu Pro Asn Asn 1820 1825 1830

Glu Asp Arg Val Arg Gly Ser Phe Ala Phe Asp Ser Pro His His 1835 1840 1845 Glu Asp Arg Val Arg Gly Ser Phe Ala Phe Asp Ser Pro His His 1835 1840 1845

Tyr Thr Pro Ile Glu Gly Thr Pro Tyr Cys Phe Ser Arg Asn Asp 1850 1855 1860 Tyr Thr Pro Ile Glu Gly Thr Pro Tyr Cys Phe Ser Arg Asn Asp 1850 1855 1860

Ser Leu Ser Ser Leu Asp Phe Asp Asp Asp Asp Val Asp Leu Ser Be Leu Be Be Leu Asp Phe Asp Asp Asp Asp Asp Val Asp Leu Ser

1865 1870 1865 1870

Arg Glu Lys Ala Glu Leu Arg Lys Ala Lys Glu Asn Lys Glu Ser 1880 1885 1890 Arg Glu Lys Wing Glu Leu Arg Lys Wing Lys Glu Asn Lys Glu Ser 1880 1885 1890

Glu Ala Lys Val Thr Ser His Thr Glu Leu Thr Ser Asn Gln Gln 1895 1900 1905 Glu Ala Lys Val Thr Ser His Thr Glu Leu Thr Ser Asn Gln Gln 1895 1900 1905

Ser Ala Asn Lys Thr Gln Ala Ile Ala Lys Gln Pro Ile Asn Arg 1910 1915 1920 Ser Ala Asn Lys Thr Gln Ile Wing Lys Gln Pro Ile Asn Arg 1910 1915 1920

Gly Gln Pro Lys Pro Ile Leu Gln Lys Gln Ser Thr Phe Pro Gln 1925 1930 1935 Gly Gln Pro Lys Pro Ile Leu Gln Lys Gln Ser Thr Phe Pro Gln 1925 1930 1935

Ser Ser Lys Asp Ile Pro Asp Arg Gly Ala Ala Thr Asp Glu Lys 1940 1945 1950 Ser Ser Lys Asp Ile Pro Asp Arg Gly Ala Wing Thr Asp Glu Lys 1940 1945 1950

Leu Gln Asn Phe Ala Ile Glu Asn Thr Pro Val Cys Phe Ser His 1955 1960 1965 Leu Gln Asn Phe Ala Ile Glu Asn Thr Pro Val Cys Phe Ser His 1955 1960 1965

Asn Ser Ser Leu Ser Ser Leu Ser Asp Ile Asp Gln Glu Asn Asn 1970 1975 1980 Asn Be Be Leu Be Be Leu Be Asp Ile Asp Gln Glu Asn Asn 1970 1975 1980

Asn Lys Glu Asn Glu Pro Ile Lys Glu Thr Glu Pro Pro Asp Ser 1985 1990 1995 Asn Lys Glu Asn Glu Pro Ile Lys Glu Thr Glu Pro Pro Asp Ser 1985 1990 1995

Gln Gly Glu Pro Ser Lys Pro Gln Ala Ser Gly Tyr Ala Pro Lys 2000 2005 2010 Gln Gly Glu Pro Ser Lys Pro Gln Ala Ser Gly Tyr Ala Pro Lys 2000 2005 2010

Ser Phe His Val Glu Asp Thr Pro Val Cys Phe Ser Arg Asn Ser 2015 2020 2025 Ser Phe His Val Glu Asp Thr Pro Val Cys Phe Ser Arg Asn Ser 2015 2020 2025

Ser Leu Ser Ser Leu Ser Ile Asp Ser Glu Asp Asp Leu Leu Gln 2030 2035 2040 Be Leu Be Be Leu Be Ile Asp Be Glu Asp Asp Leu Leu Gln 2030 2035 2040

Glu Cys Ile Ser Ser Ala Met Pro Lys Lys Lys Lys Pro Ser Arg 2045 2050 2055 Glu Cys Ile Ser Ser Ala Met Pro Lys Lys Lys Lys Pro Ser Arg 2045 2050 2055

Leu Lys Gly Asp Asn Glu Lys His Ser Pro Arg Asn Met Gly Gly 2060 2065 2070 Leu Lys Gly Asp Asn Glu Lys His Ser Pro Arg Asn Met Gly Gly 2060 2065 2070

Ile Leu Gly Glu Asp Leu Thr Leu Asp Leu Lys Asp Ile Gln Arg 2075 2080 2085 Ile Leu Gly Glu Asp Leu Thr Leu Asp Leu Lys Asp Ile Gln Arg 2075 2080 2085

Pro Asp Ser Glu His Gly Leu Ser Pro Asp Ser Glu Asn Phe Asp 2090 2095 2100 Pro Asp Ser Glu His Gly Leu Ser Pro Asp Ser Glu Asn Phe Asp 2090 2095 2100

Trp Lys Ala Ile Gln Glu Gly Ala Asn Ser Ile Val Ser Ser Leu 2105 2110 2115 Trp Lys Ile Gln Glu Gly Wing Asn Ser Ile Val Ser Ser Leu 2105 2110 2115

His Gln Ala Ala Ala Ala Ala Cys Leu Ser Arg Gln Ala Ser Ser 2120 2125 2130 His Gln Wing Wing Wing Wing Cys Leu Ser Arg Gln Wing Being Ser 2120 2125 2130

Asp Ser Asp Ser Ile Leu Ser Leu Lys Ser Gly Ile Ser Leu Gly 2135 2140 2145 Asp Be Asp Be Ile Leu Be Leu Lys Be Gly Ile Be Leu Gly 2135 2140 2145

Ser Pro Phe His Leu Thr Pro Asp Gln Glu Glu Lys Pro Phe Thr 2150 2155 2160 Ser Pro Phe His Leu Thr Pro Asp Gln Glu Glu Lys Pro Phe Thr 2150 2155 2160

Ser Asn Lys Gly Pro Arg Ile Leu Lys Pro Gly Glu Lys Ser Thr 2165 2170 2175 Ser Asn Lys Gly Pro Arg Ile Leu Lys Pro Gly Glu Lys Ser Thr 2165 2170 2175

Leu Glu Thr Lys Lys Ile Glu Ser Glu Ser Lys Gly Ile Lys Gly 2180 2185 2190 Leu Glu Thr Lys Lys Ile Glu Ser Glu Ser Lys Gly Ile Lys Gly 2180 2185 2190

Gly Lys Lys Val Tyr Lys Ser Leu Ile Thr Gly Lys Val Arg Ser 2195 2200 2205 Asn Ser Glu Ile Ser Gly Gln Met Lys Gln Pro Leu Gln Ala Asn 2210 2215 2220 Gly Lys Lys Val Tyr Lys Ser Leu Ile Thr Gly Lys Val Arg Ser 2195 2200 2205 Asn Ser Glu Ile Ser Gly Gln Met Lys Gln Pro Leu Gln Wing Asn 2210 2215 2220

Met Pro Ser Ile Ser Arg Gly Arg Thr Met Ile His Ile Pro Gly 2225 2230 2235 Met Pro Ser Ile Ser Arg Gly Arg Thr Met Ile His Ile Pro Gly 2225 2230 2235

Val Arg Asn Ser Ser Ser Ser Thr Ser Pro Val Ser Lys Lys Gly 2240 2245 2250 Val Arg Asn Be Be Be Be Thr Be Pro Val Be Lys Lys Gly 2240 2245 2250

Pro Pro Leu Lys Thr Pro Ala Ser Lys Ser Pro Ser Glu Gly Gln 2255 2260 2265 Pro Pro Leu Lys Thr Pro Ala Ser Lys Ser Pro Ser Glu Gly Gln 2255 2260 2265

Thr Ala Thr Thr Ser Pro Arg Gly Ala Lys Pro Ser Val Lys Ser 2270 2275 2280 Thr Ala Thr Thr Ser Pro Arg Gly Ala Lys Pro Ser Val Lys Ser 2270 2275 2280

Glu Leu Ser Pro Val Ala Arg Gln Thr Ser Gln Ile Gly Gly Ser 2285 2290 2295 Glu Leu Ser Pro Val Ala Arg Gln Thr Ser Gln Ile Gly Gly Ser 2285 2290 2295

Ser Lys Ala Pro Ser Arg Ser Gly Ser Arg Asp Ser Thr Pro Ser 2300 2305 2310 Ser Lys Ala Pro Ser Arg Ser Gly Ser Arg Asp Ser Thr Pro Ser 2300 2305 2310

Arg Pro Ala Gln Gln Pro Leu Ser Arg Pro Ile Gln Ser Pro Gly 2315 2320 2325 Arg Pro Wing Gln Gln Pro Leu Ser Arg Pro Ile Gln Ser Pro Gly 2315 2320 2325

Arg Asn Ser Ile Ser Pro Gly Arg Asn Gly Ile Ser Pro Pro Asn 2330 2335 2340 Arg Asn Ser Ile Ser Pro Gly Arg Asn Gly Ile Ser Pro Pro Asn 2330 2335 2340

Lys Leu Ser Gln Leu Pro Arg Thr Ser Ser Pro Ser Thr Ala Ser 2345 2350 2355 Lys Leu Ser Gln Leu Pro Arg Thr Ser Ser Pro Ser Thr Ala Ser 2345 2350 2355

Thr Lys Ser Ser Gly Ser Gly Lys Met Ser Tyr Thr Ser Pro Gly 2360 2365 2370 Thr Lys Ser Ser Gly Ser Gly Lys Met Ser Tyr Thr Ser Pro Gly 2360 2365 2370

Arg Gln Met Ser Gln Gln Asn Leu Thr Lys Gln Thr Gly Leu Ser 2375 2380 2385 Arg Gln Met Ser Gln Gln Asn Leu Thr Lys Gln Thr Gly Leu Ser 2375 2380 2385

Lys Asn Ala Ser Ser Ile Pro Arg Ser Glu Ser Ala Ser Lys Gly 2390 2395 2400 Lys Asn Wing Be Being Ile Pro Arg Be Glu Be Wing Being Lys Gly 2390 2395 2400

Leu Asn Gln Met Asn Asn Gly Asn Gly Ala Asn Lys Lys Val Glu 2405 2410 2415 Leu Asn Gln Met Asn Asn Gly Asn Gly Ala Asn Lys Lys Val Glu 2405 2410 2415

Leu Ser Arg Met Ser Ser Thr Lys Ser Ser Gly Ser Glu Ser Asp 2420 2425 2430 Leu Be Arg Met Be Be Thr Lys Be Be Gly Ser Glu Be Asp 2420 2425 2430

Arg Ser Glu Arg Pro Val Leu Val Arg Gln Ser Thr Phe Ile Lys 2435 2440 2445 Arg Ser Glu Arg Pro Val Leu Val Arg Gln Ser Thr Phe Ile Lys 2435 2440 2445

Glu Ala Pro Ser Pro Thr Leu Arg Arg Lys Leu Glu Glu Ser Ala 2450 2455 2460 Glu Ala Pro Ser Pro Thr Leu Arg Arg Lys Leu Glu Glu Ser Ala 2450 2455 2460

Ser Phe Glu Ser Leu Ser Pro Ser Ser Arg Pro Ala Ser Pro Thr 2465 2470 2475 Be Phe Glu Be Leu Be Pro Be Be Arg Pro Wing Be Pro Thr 2465 2470 2475

Arg Ser Gln Ala Gln Thr Pro Val Leu Ser Pro Ser Leu Pro Asp 2480 2485 2490 Arg Ser Gln Ala Gln Thr Pro Val Leu Ser Pro Ser Leu Pro Asp 2480 2485 2490

Met Ser Leu Ser Thr His Ser Ser Val Gln Ala Gly Gly Trp Arg 2495 2500 2505 Met Ser Leu Ser Thr His Ser Ser Val Gln Ala Gly Gly Trp Arg 2495 2500 2505

Lys Leu Pro Pro Asn Leu Ser Pro Thr Ile Glu Tyr Asn Asp Gly 2510 2515 2520 Lys Leu Pro Pro Asn Leu Ser Pro Thr Ile Glu Tyr Asn Asp Gly 2510 2515 2520

Arg Pro Ala Lys Arg His Asp Ile Ala Arg Ser His Ser Glu Ser 2525 2530 2535 Arg Pro Ala Lys Arg His Asp Ile Ala Arg Ser His Ser Glu Ser 2525 2530 2535

Pro Ser Arg Leu Pro Ile Asn Arg Ser Gly Thr Trp Lys Arg Glu 2540 2545 2550 Pro Ser Arg Leu Pro Ile Asn Arg Ser Gly Thr Trp Lys Arg Glu 2540 2545 2550

His Ser Lys His Ser Ser Ser Leu Pro Arg Val Ser Thr Trp Arg 2555 2560 2565 His Ser Lys His Ser Ser Ser Leu Pro Arg Val Ser Thr Trp Arg 2555 2560 2565

Arg Thr Gly Ser Ser Ser Ser Ile Leu Ser Ala Ser Ser Glu Ser 2570 2575 2580 Arg Thr Gly Be Be Be Be Ile Leu Be Wing Be Be Glu Be 2570 2575 2580

Ser Glu Lys Ala Lys Ser Glu Asp Glu Lys His Val Asn Ser Ile 2585 2590 2595 Ser Glu Lys Ala Lys Ser Glu Asp Glu Lys His Val Asn Ser Ile 2585 2590 2595

Ser Gly Thr Lys Gln Ser Lys Glu Asn Gln Val Ser Ala Lys Gly 2600 2605 2610 Ser Gly Thr Lys Gln Ser Lys Glu Asn Gln Val Ser Ala Lys Gly 2600 2605 2610

Thr Trp Arg Lys Ile Lys Glu Asn Glu Phe Ser Pro Thr Asn Ser 2615 2620 2625 Thr Trp Arg Lys Ile Lys Glu Asn Glu Phe Ser Pro Thr Asn Ser 2615 2620 2625

Thr Ser Gln Thr Val Ser Ser Gly Ala Thr Asn Gly Ala Glu Ser 2630 2635 2640 Thr Ser Gln Thr Val Ser Ser Gly Ala Thr Asn Gly Ala Glu Ser 2630 2635 2640

Lys Thr Leu Ile Tyr Gln Met Ala Pro Ala Val Ser Lys Thr Glu 2645 2650 2655 Lys Thr Leu Ile Tyr Gln Met Wing Pro Wing Val Ser Lys Thr Glu 2645 2650 2655

Asp Val Trp Val Arg Ile Glu Asp Cys Pro Ile Asn Asn Pro Arg 2660 2665 2670 Asp Val Trp Val Arg Ile Glu Asp Cys Pro Ile Asn Asn Pro Arg 2660 2665 2670

Ser Gly Arg Ser Pro Thr Gly Asn Thr Pro Pro Val Ile Asp Ser 2675 2680 2685 Ser Gly Arg Ser Pro Thr Gly Asn Thr Pro Pro Val Ile Asp Ser 2675 2680 2685

Val Ser Glu Lys Ala Asn Pro Asn Ile Lys Asp Ser Lys Asp Asn 2690 2695 2700 Val Ser Glu Lys Wing Asn Pro Asn Ile Lys Asp Ser Lys Asp Asn 2690 2695 2700

Gln Ala Lys Gln Asn Val Gly Asn Gly Ser Val Pro Met Arg Thr 2705 2710 2715 Gln Wing Lys Gln Asn Val Gly Asn Gly Ser Val Pro Met Arg Thr 2705 2710 2715

Val Gly Leu Glu Asn Arg Leu Asn Ser Phe Ile Gln Val Asp Ala 2720 2725 2730 Val Gly Leu Glu Asn Arg Leu Asn Ser Phe Ile Gln Val Asp Wing 2720 2725 2730

Pro Asp Gln Lys Gly Thr Glu Ile Lys Pro Gly Gln Asn Asn Pro 2735 2740 2745 Pro Asp Gln Lys Gly Thr Glu Ile Lys Pro Gly Gln Asn Asn Pro 2735 2740 2745

Val Pro Val Ser Glu Thr Asn Glu Ser Ser Ile Val Glu Arg Thr 2750 2755 2760 Val Pro Val Ser Glu Thr Asn Glu Ser Ser Ile Val Glu Arg Thr 2750 2755 2760

Pro Phe Ser Ser Ser Ser Ser Ser Lys His Ser Ser Pro Ser Gly 2765 2770 2775 Pro Phe Be Be Be Be Be Be Lys His Be Be Pro Be Gly 2765 2770 2775

Thr Val Ala Ala Arg Val Thr Pro Phe Asn Tyr Asn Pro Ser Pro 2780 2785 2790 Thr Val Wing Wing Arg Val Thr Pro Phe Asn Tyr Asn Pro Ser Pro 2780 2785 2790

Arg Lys Ser Ser Ala Asp Ser Thr Ser Ala Arg Pro Ser Gln Ile 2795 2800 2805 Arg Lys Ser Ser Ala Asp Ser Thr Ser Ala Arg Pro Ser Gln Ile 2795 2800 2805

Pro Thr Pro Val Asn Asn Asn Thr Lys Lys Arg Asp Ser Lys Thr 2810 2815 2820 Pro Thr Pro Val Asn Asn Asn Thr Lys Lys Arg Asp Ser Lys Thr 2810 2815 2820

Asp Ser Thr Glu Ser Ser Gly Thr Gln Ser Pro Lys Arg His Ser 2825 2830 2835 Asp Ser Thr Glu Ser Ser Gly Thr Gln Ser Pro Lys Arg His Ser 2825 2830 2835

Gly Ser Tyr Leu Val Thr Ser Val 2840 Gly Ser Tyr Leu Val Thr Ser Val 2840

<210> 40 <210> 40

<211> 3056 <211> 3056

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 40<400> 40

Met Ser Leu Val Leu Asn Asp Leu Leu Ile Cys Cys Arg Gln Leu Met Ser Leu Val Leu Asn Asp Leu Leu Ile Cys Cys Arg Gln Leu

1 5 10 15 1 5 10 15

Glu His Asp Arg Ala Thr Glu Arg Lys Lys Glu Val Glu Lys Phe 20 25 30 Glu His Asp Arg Ala Thr Glu Arg Lys Lys Glu Val Glu Lys Phe 20 25 30

Lys Arg Leu Ile Arg Asp Pro Glu Thr Ile Lys His Leu Asp Arg 35 40 45 Lys Arg Leu Ile Arg Asp Pro Glu Thr Ile Lys His Leu Asp Arg 35 40 45

His Ser Asp Ser Lys Gln Gly Lys Tyr Leu Asn Trp Asp Ala Val 50 55 60 His Ser Asp Ser Lys Gln Gly Lys Tyr Leu Asn Trp Asp Ala Val 50 55 60

Phe Arg Phe Leu Gln Lys Tyr Ile Gln Lys Glu Thr Glu Cys Leu 65 70 75 Phe Arg Phe Leu Gln Lys Tyr Ile Gln Lys Glu Thr Glu Cys Leu 65 70 75

Arg Ile Ala Lys Pro Asn Val Ser Ala Ser Thr Gln Ala Ser Arg 80 85 90 Arg Ile Ala Lys Pro Asn Val Ser Ala Ser Thr Gln Ala Ser Arg 80 85 90

Gln Lys Lys Met Gln Glu Ile Ser Ser Leu Val Lys Tyr Phe Ile 95 100 105 Gln Lys Lys Met Gln Glu Ile Ser Ser Leu Val Lys Tyr Phe Ile 95 100 105

Lys Cys Ala Asn Arg Arg Ala Pro Arg Leu Lys Cys Gln Glu Leu 110 115 120 Lys Cys Wing Asn Arg Arg Wing Pro Arg Leu Lys Cys Gln Glu Leu 110 115 120

Leu Asn Tyr Ile Met Asp Thr Val Lys Asp Ser Ser Asn Gly Ala 125 130 135 Leu Asn Tyr Ile Met Asp Thr Val Lys Asp Ser Ser Asn Gly Ala 125 130 135

Ile Tyr Gly Ala Asp Cys Ser Asn Ile Leu Leu Lys Asp Ile Leu 140 145 150 Ile Tyr Gly Ala Asp Cys Ser Asn Ile Leu Leu Lys Asp Ile Leu 140 145 150

Ser Val Arg Lys Tyr Trp Cys Glu Ile Ser Gln Gln Gln Trp Leu 155 160 165 Ser Val Arg Lys Tyr Trp Cys Glu Ile Ser Gln Gln Gln Trp Leu 155 160 165

Glu Leu Phe Ser Val Tyr Phe Arg Leu Tyr Leu Lys Pro Ser Gln 170 175 180 Glu Leu Phe Ser Val Tyr Phe Arg Leu Tyr Leu Lys Pro Ser Gln 170 175 180

Asp Val His Arg Val Leu Val Ala Arg Ile Ile His Ala Val Thr 185 190 195 Asp Val His Arg Val Leu Val Ala Arg Ile Ile His Ala Val Thr 185 190 195

Lys Gly Cys Cys Ser Gln Thr Asp Gly Leu Asn Ser Lys Phe Leu 200 205 210 Lys Gly Cys Cys Ser Gln Thr Asp Gly Leu Asn Ser Lys Phe Leu 200 205 210

Asp Phe Phe Ser Lys Ala Ile Gln Cys Ala Arg Gln Glu Lys Ser 215 220 225 Asp Phe Phe Ser Lys Ile Wing Gln Cys Wing Arg Gln Glu Lys Ser 215 220 225

Ser Ser Gly Leu Asn His Ile Leu Ala Ala Leu Thr Ile Phe Leu 230 235 240 Be Ser Gly Leu Asn His Ile Leu Ala Wing Leu Thr Ile Phe Leu 230 235 240

Lys Thr Leu Ala Val Asn Phe Arg Ile Arg Val Cys Glu Leu Gly 245 250 255 Lys Thr Leu Wing Val Asn Phe Arg Ile Arg Val Cys Glu Leu Gly 245 250 255

Asp Glu Ile Leu Pro Thr Leu Leu Tyr Ile Trp Thr Gln His Arg 260 265 270 Asp Glu Ile Leu Pro Thr Leu Leu Tyr Ile Trp Thr Gln His Arg 260 265 270

Leu Asn Asp Ser Leu Lys Glu Val Ile Ile Glu Leu Phe Gln Leu 275 280 285 Leu Asn Asp Ser Leu Lys Glu Val Ile Ile Glu Leu Phe Gln Leu 275 280 285

Gln Ile Tyr Ile His His Pro Lys Gly Ala Lys Thr Gln Glu Lys 290 295 300 Gln Ile Tyr Ile His His Pro Lys Gly Ala Lys Thr Gln Glu Lys 290 295 300

Gly Ala Tyr Glu Ser Thr Lys Trp Arg Ser Ile Leu Tyr Asn Leu 305 310 315 Gly Ala Tyr Glu Ser Thr Lys Trp Arg Ser Ile Leu Tyr Asn Leu 305 310 315

Tyr Asp Leu Leu Val Asn Glu Ile Ser His Ile Gly Ser Arg Gly 320 325 330 Tyr Asp Leu Leu Val Asn Glu Ile Ser His Ile Gly Ser Arg Gly 320 325 330

Lys Tyr Ser Ser Gly Phe Arg Asn Ile Ala Val Lys Glu Asn Leu 335 340 Lys Tyr Ser Ser Gly Phe Arg Asn Ile Wing Val Lys Glu Asn Leu 335 340

Ile Glu Leu Met Ala Asp Ile Cys His Gln Val Phe Asn Glu Asp 350 355 Ile Glu Leu Met Wing Asp Ile Cys His Gln Val Phe Asn Glu Asp 350 355

Thr Arg Ser Leu Glu Ile Ser Gln Ser Tyr Thr Thr Thr Gln Arg 365 370 375 Thr Arg Ser Leu Glu Ile Ser Gln Ser Tyr Thr Thr Thr Gln Arg 365 370 375

Glu Ser Ser Asp Tyr Ser Val Pro Cys Lys Arg Lys Lys Ile Glu 380 385 390 Glu Ser Ser Asp Tyr Ser Val Pro Cys Lys Arg Lys Lys Ile Glu 380 385 390

Leu Gly Trp Glu Val Ile Lys Asp His Leu Gln Lys Ser Gln Asn 395 400 405 Leu Gly Trp Glu Val Ile Lys Asp His Leu Gln Lys Ser Gln Asn 395 400 405

Asp Phe Asp Leu Val Pro Trp Leu Gln Ile Ala Thr Gln Leu Ile 410 415 420 Asp Phe Asp Leu Val Pro Trp Leu Gln Ile Wing Thr Gln Leu Ile 410 415 420

Ser Lys Tyr Pro Ala Ser Leu Pro Asn Cys Glu Leu Ser Pro Leu 425 430 435 Ser Lys Tyr Pro Ala Ser Leu Pro Asn Cys Glu Leu Ser Pro Leu 425 430 435

Leu Met Ile Leu Ser Gln Leu Leu Pro Gln Gln Arg His Gly Glu 440 445 450 Leu Met Ile Leu Ser Gln Leu Leu Pro Gln Gln Arg His Gly Glu 440 445 450

Arg Thr Pro Tyr Val Leu Arg Cys Leu Thr Glu Val Ala Leu Cys 455 460 465 Arg Thr Pro Tyr Val Leu Arg Cys Leu Thr Glu Val Ala Leu Cys 455 460 465

Gln Asp Lys Arg Ser Asn Leu Glu Ser Ser Gln Lys Ser Asp Leu 470 475 480 Gln Asp Lys Arg Be Asn Leu Glu Ser Be Gln Lys Be Asp Leu 470 475 480

Leu Lys Leu Trp Asn Lys Ile Trp Cys Ile Thr Phe Arg Gly Ile 485 490 495 Leu Lys Leu Trp Asn Lys Ile Trp Cys Ile Thr Phe Arg Gly Ile 485 490 495

Ser Ser Glu Gln Ile Gln Ala Glu Asn Phe Gly Leu Leu Gly Ala 500 505 510 Be Ser Glu Gln Ile Gln Ala Glu Asn Phe Gly Leu Leu Gly Ala 500 505 510

Ile Ile Gln Gly Ser Leu Val Glu Val Asp Arg Glu Phe Trp Lys 515 520 525 Ile Ile Gln Gly Ser Leu Val Glu Val Asp Arg Glu Phe Trp Lys 515 520 525

Leu Phe Thr Gly Ser Ala Cys Arg Pro Ser Cys Pro Ala Val Cys 530 535 540 Leu Phe Thr Gly Ser Ala Cys Arg Pro Ser Cys Pro Ala Val Cys 530 535 540

Cys Leu Thr Leu Ala Leu Thr Thr Ser Ile Val Pro Gly Thr Val 545 550 555 Cys Leu Thr Leu Ala Leu Thr Thr Ser Ile Val Pro Gly Thr Val 545 550 555

Lys Met Gly Ile Glu Gln Asn Met Cys Glu Val Asn Arg Ser Phe 560 565 570 Lys Met Gly Ile Glu Gln Asn Met Cys Glu Val Asn Arg Ser Phe 560 565 570

Ser Leu Lys Glu Ser Ile Met Lys Trp Leu Leu Phe Tyr Gln Leu 575 580 585 Ser Leu Lys Glu Ser Ile Met Lys Trp Leu Leu Phe Tyr Gln Leu 575 580 585

Glu Gly Asp Leu Glu Asn Ser Thr Glu Val Pro Pro Ile Leu His 590 595 600 Glu Gly Asp Leu Glu Asn Ser Thr Glu Val Pro Pro Ile Leu His 590 595 600

Ser Asn Phe Pro His Leu Val Leu Glu Lys Ile Leu Val Ser Leu 605 610 615 Ser Asn Phe Pro His Leu Val Leu Glu Lys Ile Leu Val Ser Leu 605 610 615

Thr Met Lys Asn Cys Lys Ala Ala Met Asn Phe Phe Gln Ser Val 620 625 630 Thr Met Lys Asn Cys Lys Wing Wing Met Asn Phe Phe Gln Ser Val 620 625 630

Pro Glu Cys Glu His His Gln Lys Asp Lys Glu Glu Leu Ser Phe 635 640 645 Pro Glu Cys Glu His His Gln Lys Asp Lys Glu Glu Leu Ser Phe 635 640 645

Ser Glu Val Glu Glu Leu Phe Leu Gln Thr Thr Phe Asp Lys Met 650 655 660 Ser Glu Val Glu Glu Leu Phe Leu Gln Thr Thr Phe Asp Lys Met 650 655 660

Asp Phe Leu Thr Ile Val Arg Glu Cys Gly Ile Glu Lys His Gln 665 670 675 Asp Phe Leu Thr Ile Val Arg Glu Cys Gly Ile Glu Lys His Gln 665 670 675

Ser Ser Ile Gly Phe Ser Val His Gln Asn Leu Lys Glu Ser Leu 680 685 Be Be Ile Gly Phe Be Val His Gln Asn Leu Lys Glu Ser Leu 680 685

Asp Arg Cys Leu Leu Gly Leu Ser Glu Gln Leu Leu Asn Asn Tyr 695 700 Asp Arg Cys Leu Leu Gly Leu Ser Glu Gln Leu Leu Asn Asn Tyr 695 700

Ser Ser Glu Ile Thr Asn Ser Glu Thr Leu Val Arg Cys Ser Arg 710 715 720 Be Ser Glu Ile Thr Asn Ser Glu Thr Leu Val Arg Cys Ser Arg 710 715 720

Leu Leu Val Gly Val Leu Gly Cys Tyr Cys Tyr Met Gly Val Ile 725 730 735 Leu Leu Val Gly Val Leu Gly Cys Tyr Cys Tyr Met Gly Val Ile 725 730 735

Ala Glu Glu Glu Ala Tyr Lys Ser Glu Leu Phe Gln Lys Ala Lys 740 745 750 Wing Glu Glu Glu Wing Tyr Lys Ser Glu Leu Phe Gln Lys Wing Lys 740 745 750

Ser Leu Met Gln Cys Ala Gly Glu Ser Ile Thr Leu Phe Lys Asn 755 760 765 Ser Leu Met Gln Cys Ala Gly Glu Ser Ile Thr Leu Phe Lys Asn 755 760 765

Lys Thr Asn Glu Glu Phe Arg Ile Gly Ser Leu Arg Asn Met Met 770 775 780 Lys Thr Asn Glu Glu Phe Arg Ile Gly Ser Leu Arg Asn Met Met 770 775 780

Gln Leu Cys Thr Arg Cys Leu Ser Asn Cys Thr Lys Lys Ser Pro 785 790 795 Gln Leu Cys Thr Arg Cys Leu Ser Asn Cys Thr Lys Lys Ser Pro 785 790 795

Asn Lys Ile Ala Ser Gly Phe Phe Leu Arg Leu Leu Thr Ser Lys 800 805 810 Asn Lys Ile Ala Ser Gly Phe Phe Leu Arg Leu Leu Thr Ser Lys 800 805 810

Leu Met Asn Asp Ile Ala Asp Ile Cys Lys Ser Leu Ala Ser Phe 815 820 825 Leu Met Asn Asp Ile Ala Asp Ile Cys Lys Ser Leu Ala Ser Phe 815 820 825

Ile Lys Lys Pro Phe Asp Arg Gly Glu Val Glu Ser Met Glu Asp 830 835 840 Ile Lys Lys Pro Phe Asp Arg Gly Glu Val Glu Ser Met Glu Asp 830 835 840

Asp Thr Asn Gly Asn Leu Met Glu Val Glu Asp Gln Ser Ser Met 845 850 855 Asp Thr Asn Gly Asn Leu Met Glu Val Glu Asp Gln Ser Ser Met 845 850 855

Asn Leu Phe Asn Asp Tyr Pro Asp Ser Ser Val Ser Asp Ala Asn 860 865 870 Asn Leu Phe Asn Asp Tyr Pro Asp Ser Ser Val Ser Asp Ala Asn 860 865 870

Glu Pro Gly Glu Ser Gln Ser Thr Ile Gly Ala Ile Asn Pro Leu 875 880 885 Glu Pro Gly Glu Ser Gln Ser Thr Ile Gly Ala Ile Asn Pro Leu 875 880 885

Ala Glu Glu Tyr Leu Ser Lys Gln Asp Leu Leu Phe Leu Asp Met 890 895 900 Wing Glu Glu Tyr Leu Ser Lys Gln Asp Leu Leu Phe Leu Asp Met 890 895 900

Leu Lys Phe Leu Cys Leu Cys Val Thr Thr Ala Gln Thr Asn Thr 905 910 915 Leu Lys Phe Leu Cys Leu Cys Val Thr Thr Wing Gln Thr Asn Thr 905 910 915

Val Ser Phe Arg Ala Ala Asp Ile Arg Arg Lys Leu Leu Met Leu 920 925 930 Val Ser Phe Arg Wing Wing Asp Ile Arg Arg Lys Leu Leu Met Leu 920 925 930

Ile Asp Ser Ser Thr Leu Glu Pro Thr Lys Ser Leu His Leu His 935 940 945 Ile Asp Ser Ser Thr Leu Glu Pro Thr Lys Ser Leu His Leu His 935 940 945

Met Tyr Leu Met Leu Leu Lys Glu Leu Pro Gly Glu Glu Tyr Pro 950 955 960 Met Tyr Leu Met Leu Leu Lys Glu Leu Pro Gly Glu Glu Tyr Pro 950 955 960

Leu Pro Met Glu Asp Val Leu Glu Leu Leu Lys Pro Leu Ser Asn 965 970 975 Leu Pro Met Glu Asp Val Leu Glu Leu Leu Lys Pro Leu Ser Asn 965 970 975

Val Cys Ser Leu Tyr Arg Arg Asp Gln Asp Val Cys Lys Thr Ile 980 985 990 Val Cys Ser Leu Tyr Arg Arg Asp Gln Asp Val Cys Lys Thr Ile 980 985 990

Leu Asn His Val Leu His Val Val Lys Asn Leu Gly Gln Ser Asn 995 1000 1005 Leu Asn His Val Leu His Val Val Lys Asn Leu Gly Gln Ser Asn 995 1000 1005

Met Asp Ser Glu Asn Thr Arg Asp Ala Gln Gly Gln Phe Leu Thr 1010 1015 1020 Met Asp Ser Glu Asn Thr Arg Asp Wing Gln Gly Gln Phe Leu Thr 1010 1015 1020

Val Ile Gly Ala Phe Trp His Leu Thr Lys Glu Arg Lys Tyr Ile Val Ile Gly Ala Phe Trp His Leu Thr Lys Glu Arg Lys Tyr Ile

1025 1030 1025 1030

Phe Ser Val Arg Met Ala Leu Val Asn Cys Leu Lys Thr Leu Leu 1040 1045 1050 Phe Ser Val Arg Met Ala Leu Val Asn Cys Leu Lys Thr Leu Leu 1040 1045 1050

Glu Ala Asp Pro Tyr Ser Lys Trp Ala Ile Leu Asn Val Met Gly 1055 1060 1065 Glu Wing Asp Pro Tyr Ser Lys Trp Wing Ile Leu Asn Val Met Gly 1055 1060 1065

Lys Asp Phe Pro Val Asn Glu Val Phe Thr Gln Phe Leu Ala Asp 1070 1075 1080 Lys Asp Phe Pro Val Asn Glu Val Phe Thr Gln Phe Leu Wing Asp 1070 1075 1080

Asn His His Gln Val Arg Met Leu Ala Ala Glu Ser Ile Asn Arg 1085 1090 1095 Asn His His Gln Val Arg Met Leu Ala Ala Glu Ser Ile Asn Arg 1085 1090 1095

Leu Phe Gln Asp Thr Lys Gly Asp Ser Ser Arg Leu Leu Lys Ala 1100 1105 1110 Leu Phe Gln Asp Thr Lys Gly Asp Ser Ser Arg Leu Leu Lys Ala 1100 1105 1110

Leu Pro Leu Lys Leu Gln Gln Thr Ala Phe Glu Asn Ala Tyr Leu 1115 1120 1125 Leu Pro Leu Lys Leu Gln Gln Thr Wing Phe Glu Asn Wing Tyr Leu 1115 1120 1125

Lys Ala Gln Glu Gly Met Arg Glu Met Ser His Ser Ala Glu Asn 1130 1135 1140 Lys Wing Gln Glu Gly Met Arg Glu Met Ser His Ser Ala Glu Asn 1130 1135 1140

Pro Glu Thr Leu Asp Glu Ile Tyr Asn Arg Lys Ser Val Leu Leu 1145 1150 1155 Pro Glu Thr Leu Asp Glu Ile Tyr Asn Arg Lys Ser Val Leu Leu 1145 1150 1155

Thr Leu Ile Ala Val Val Leu Ser Cys Ser Pro Ile Cys Glu Lys 1160 1165 1170 Thr Leu Ile Wing Val Val Leu Ser Cys Ser Pro Ile Cys Glu Lys 1160 1165 1170

Gln Ala Leu Phe Ala Leu Cys Lys Ser Val Lys Glu Asn Gly Leu 1175 1180 1185 Gln Ala Leu Phe Ala Leu Cys Lys Ser Val Lys Glu Asn Gly Leu 1175 1180 1185

Glu Pro His Leu Val Lys Lys Val Leu Glu Lys Val Ser Glu Thr 1190 1195 1200 Glu Pro His Leu Val Lys Lys Val Leu Glu Lys Val Ser Glu Thr 1190 1195 1200

Phe Gly Tyr Arg Arg Leu Glu Asp Phe Met Ala Ser His Leu Asp 1205 1210 1215 Phe Gly Tyr Arg Arg Leu Glu Asp Phe Met Ala Ser His Leu Asp 1205 1210 1215

Tyr Leu Val Leu Glu Trp Leu Asn Leu Gln Asp Thr Glu Tyr Asn 1220 1225 1230 Tyr Leu Val Leu Glu Trp Leu Asn Leu Gln Asp Thr Glu Tyr Asn 1220 1225 1230

Leu Ser Ser Phe Pro Phe Ile Leu Leu Asn Tyr Thr Asn Ile Glu 1235 1240 1245 Leu Ser Ser Phe Pro Phe Ile Leu Leu Asn Tyr Thr Asn Ile Glu 1235 1240 1245

Asp Phe Tyr Arg Ser Cys Tyr Lys Val Leu Ile Pro His Leu Val 1250 1255 1260 Asp Phe Tyr Arg Ser Cys Tyr Lys Val Leu Ile Pro His Leu Val 1250 1255 1260

Ile Arg Ser His Phe Asp Glu Val Lys Ser Ile Ala Asn Gln Ile 1265 1270 1275 Ile Arg Ser His Phe Asp Glu Val Lys Ser Ile Ala Asn Gln Ile 1265 1270 1275

Gln Glu Asp Trp Lys Ser Leu Leu Thr Asp Cys Phe Pro Lys Ile 1280 1285 1290 Gln Glu Asp Trp Lys Ser Leu Leu Thr Asp Cys Phe Pro Lys Ile 1280 1285 1290

Leu Val Asn Ile Leu Pro Tyr Phe Ala Tyr Glu Gly Thr Arg Asp 1295 1300 1305 Leu Val Asn Ile Leu Pro Tyr Phe Ala Tyr Glu Gly Thr Arg Asp 1295 1300 1305

Ser Gly Met Ala Gln Gln Arg Glu Thr Ala Thr Lys Val Tyr Asp 1310 1315 1320 Ser Gly Met Wing Gln Gln Arg Glu Thr Wing Thr Lys Val Tyr Asp 1310 1315 1320

Met Leu Lys Ser Glu Asn Leu Leu Gly Lys Gln Ile Asp His Leu 1325 1330 1335 Met Leu Lys Ser Glu Asn Leu Leu Gly Lys Gln Ile Asp His Leu 1325 1330 1335

Phe Ile Ser Asn Leu Pro Glu Ile Val Val Glu Leu Leu Met Thr 1340 1345 1350 Phe Ile Ser Asn Leu Pro Glu Ile Val Val Glu Leu Leu Met Thr 1340 1345 1350

Leu His Glu Pro Ala Asn Ser Ser Ala Ser Gln Ser Thr Asp Leu 1355 1360 1365 Cys Asp Phe Ser Gly Asp Leu Asp Pro Ala Pro Asn Pro Pro His 1370 1375 1380 Leu His Glu Pro Wing Asn Be Be Wing Be Gln Be Thr Asp Leu 1355 1360 1365 Cys Asp Phe Be Gly Asp Leu Asp Pro Wing Pro Asn Pro Pro His 1370 1375 1380

Phe Pro Ser His Val Ile Lys Ala Thr Phe Ala Tyr Ile Ser Asn 1385 1390 1395 Phe Pro Ser His Val Ile Lys Ala Thr Phe Ala Tyr Ile Ser Asn 1385 1390 1395

Cys His Lys Thr Lys Leu Lys Ser Ile Leu Glu Ile Leu Ser Lys 1400 1405 1410 Cys His Lys Thr Lys Leu Lys Ser Ile Leu Glu Ile Leu Ser Lys 1400 1405 1410

Ser Pro Asp Ser Tyr Gln Lys Ile Leu Leu Ala Ile Cys Glu Gln 1415 1420 1425 Ser Pro Asp Ser Tyr Gln Lys Ile Leu Leu Ile Wing Cys Glu Gln 1415 1420 1425

Ala Ala Glu Thr Asn Asn Val Tyr Lys Lys His Arg Ile Leu Lys 1430 1435 1440 Wing Wing Glu Thr Asn Asn Val Tyr Lys Lys His Arg Ile Leu Lys 1430 1435 1440

Ile Tyr His Leu Phe Val Ser Leu Leu Leu Lys Asp Ile Lys Ser 1445 1450 1455 Ile Tyr His Leu Phe Val Ser Leu Leu Leu Lys Asp Ile Lys Ser 1445 1450 1455

Gly Leu Gly Gly Ala Trp Ala Phe Val Leu Arg Asp Val Ile Tyr 1460 1465 1470 Gly Leu Gly Gly Wing Trp Wing Phe Val Leu Arg Asp Val Ile Tyr 1460 1465 1470

Thr Leu Ile His Tyr Ile Asn Gln Arg Pro Ser Cys Ile Met Asp 1475 1480 1485 Thr Leu Ile His Tyr Ile Asn Gln Arg Pro Ser Cys Ile Met Asp 1475 1480 1485

Val Ser Leu Arg Ser Phe Ser Leu Cys Cys Asp Leu Leu Ser Gln 1490 1495 1500 Val Ser Leu Arg Ser Phe Ser Leu Cys Cys Asp Leu Leu Ser Gln 1490 1495 1500

Val Cys Gln Thr Ala Val Thr Tyr Cys Lys Asp Ala Leu Glu Asn 1505 1510 1515 Val Cys Gln Thr Wing Val Thr Tyr Cys Lys Asp Wing Leu Glu Asn 1505 1510 1515

His Leu His Val Ile Val Gly Thr Leu Ile Pro Leu Val Tyr Glu 1520 1525 1530 His Leu His Val Ile Val Gly Thr Leu Ile Pro Leu Val Tyr Glu 1520 1525 1530

Gln Val Glu Val Gln Lys Gln Val Leu Asp Leu Leu Lys Tyr Leu 1535 1540 1545 Gln Val Glu Val Gln Lys Gln Val Leu Asp Leu Leu Lys Tyr Leu 1535 1540 1545

Val Ile Asp Asn Lys Asp Asn Glu Asn Leu Tyr Ile Thr Ile Lys 1550 1555 1560 Val Ile Asp Asn Lys Asp Asn Glu Asn Leu Tyr Ile Thr Ile Lys 1550 1555 1560

Leu Leu Asp Pro Phe Pro Asp His Val Val Phe Lys Asp Leu Arg 1565 1570 1575 Leu Leu Asp Pro Phe Pro Asp His Val Val Phe Lys Asp Leu Arg 1565 1570 1575

Ile Thr Gln Gln Lys Ile Lys Tyr Ser Arg Gly Pro Phe Ser Leu 1580 1585 1590 Ile Thr Gln Gln Lys Ile Lys Tyr Ser Arg Gly Pro Phe Ser Leu 1580 1585 1590

Leu Glu Glu Ile Asn His Phe Leu Ser Val Ser Val Tyr Asp Ala 1595 1600 1605 Leu Glu Glu Ile Asn His Phe Leu Ser Val Ser Val Tyr Asp Ala 1595 1600 1605

Leu Pro Leu Thr Arg Leu Glu Gly Leu Lys Asp Leu Arg Arg Gln 1610 1615 1620 Leu Pro Leu Thr Arg Leu Glu Gly Leu Lys Asp Leu Arg Arg Gln 1610 1615 1620

Leu Glu Leu His Lys Asp Gln Met Val Asp Ile Met Arg Ala Ser 1625 1630 1635 Leu Glu Leu His Lys Asp Gln Met Val Asp Ile Met Arg Ala Ser 1625 1630 1635

Gln Asp Asn Pro Gln Asp Gly Ile Met Val Lys Leu Val Val Asn 1640 1645 1650 Gln Asp Asn Pro Gln Asp Gly Ile Met Val Lys Leu Val Val Asn 1640 1645 1650

Leu Leu Gln Leu Ser Lys Met Ala Ile Asn His Thr Gly Glu Lys 1655 1660 1665 Leu Leu Gln Leu Ser Lys Met Wing Ile Asn His Thr Gly Glu Lys 1655 1660 1665

Glu Val Leu Glu Ala Val Gly Ser Cys Leu Gly Glu Val Gly Pro 1670 1675 1680 Glu Val Leu Glu Ala Val Gly Ser Cys Leu Gly Glu Val Gly Pro 1670 1675 1680

Ile Asp Phe Ser Thr Ile Ala Ile Gln His Ser Lys Asp Ala Ser 1685 1690 1695 Ile Asp Phe Ser Thr Ile Ala Ile Gln His Ser Lys Asp Ala Ser 1685 1690 1695

Tyr Thr Lys Ala Leu Lys Leu Phe Glu Asp Lys Glu Leu Gln Trp 1700 1705 1710 Thr Phe Ile Met Leu Thr Tyr Leu Asn Asn Thr Leu Val Glu Asp 1715 1720 1725 Tyr Thr Lys Ala Leu Lys Leu Phe Glu Asp Lys Glu Leu Gln Trp 1700 1705 1710 Thr Phe Ile Met Leu Thr Tyr Leu Asn Asn Thr Leu Val Glu Asp 1715 1720 1725

Cys Val Lys Val Arg Ser Ala Ala Val Thr Cys Leu Lys Asn Ile 1730 1735 1740 Cys Val Lys Val Arg Ser Wing Val Val Thr Cys Leu Lys Asn Ile 1730 1735 1740

Leu Ala Thr Lys Thr Gly His Ser Phe Trp Glu Ile Tyr Lys Met 1745 1750 1755 Leu Ala Thr Lys Thr Gly His Ser Phe Trp Glu Ile Tyr Lys Met 1745 1750 1755

Thr Thr Asp Pro Met Leu Ala Tyr Leu Gln Pro Phe Arg Thr Ser 1760 1765 1770 Thr Thr Asp Pro Met Leu Wing Tyr Leu Gln Pro Phe Arg Thr Ser 1760 1765 1770

Arg Lys Lys Phe Leu Glu Val Pro Arg Phe Asp Lys Glu Asn Pro 1775 1780 1785 Arg Lys Lys Phe Leu Glu Val Pro Arg Phe Asp Lys Glu Asn Pro 1775 1780 1785

Phe Glu Gly Leu Asp Asp Ile Asn Leu Trp Ile Pro Leu Ser Glu 1790 1795 1800 Phe Glu Gly Leu Asp Asp Ile Asn Leu Trp Ile Pro Leu Ser Glu 1790 1795 1800

Asn His Asp Ile Trp Ile Lys Thr Leu Thr Cys Ala Phe Leu Asp 1805 1810 1815 Asn His Asp Ile Trp Ile Lys Thr Leu Thr Cys Ala Phe Leu Asp 1805 1810 1815

Ser Gly Gly Thr Lys Cys Glu Ile Leu Gln Leu Leu Lys Pro Met 1820 1825 1830 Ser Gly Gly Thr Lys Cys Glu Ile Leu Gln Leu Leu Lys Pro Met 1820 1825 1830

Cys Glu Val Lys Thr Asp Phe Cys Gln Thr Val Leu Pro Tyr Leu 1835 1840 1845 Cys Glu Val Lys Thr Asp Phe Cys Gln Thr Val Leu Pro Tyr Leu 1835 1840 1845

Ile His Asp Ile Leu Leu Gln Asp Thr Asn Glu Ser Trp Arg Asn 1850 1855 1860 Ile His Asp Ile Leu Leu Gln Asp Thr Asn Glu Ser Trp Arg Asn 1850 1855 1860

Leu Leu Ser Thr His Val Gln Gly Phe Phe Thr Ser Cys Leu Arg 1865 1870 1875 Leu Leu Ser Thr His Val Gln Gly Phe Phe Thr Ser Cys Leu Arg 1865 1870 1875

His Phe Ser Gln Thr Ser Arg Ser Thr Thr Pro Ala Asn Leu Asp 1880 1885 1890 His Phe Ser Gln Thr Ser Arg Ser Thr Thr Pro Ala Asn Leu Asp 1880 1885 1890

Ser Glu Ser Glu His Phe Phe Arg Cys Cys Leu Asp Lys Lys Ser 1895 1900 1905 Ser Glu Ser Glu His Phe Phe Arg Cys Cys Leu Asp Lys Lys Ser 1895 1900 1905

Gln Arg Thr Met Leu Ala Val Val Asp Tyr Met Arg Arg Gln Lys 1910 1915 1920 Gln Arg Thr Met Leu Wing Val Val Asp Tyr Met Arg Arg Gln Lys 1910 1915 1920

Arg Pro Ser Ser Gly Thr Ile Phe Asn Asp Ala Phe Trp Leu Asp 1925 1930 1935 Arg Pro Ser Ser Gly Thr Ile Phe Asn Asp Ala Phe Trp Leu Asp 1925 1930 1935

Leu Asn Tyr Leu Glu Val Ala Lys Val Ala Gln Ser Cys Ala Ala 1940 1945 1950 Leu Asn Tyr Leu Glu Val Wing Lys Val Wing Gln Ser Cys Wing Wing 1940 1945 1950

His Phe Thr Ala Leu Leu Tyr Ala Glu Ile Tyr Ala Asp Lys Lys 1955 1960 1965 His Phe Thr Ala Leu Leu Tyr Ala Glu Ile Tyr Ala Asp Lys Lys 1955 1960 1965

Ser Met Asp Asp Gln Glu Lys Arg Ser Leu Ala Phe Glu Glu Gly 1970 1975 1980 Ser Met Asp Asp Gln Glu Lys Arg Ser Leu Ala Phe Glu Glu Gly 1970 1975 1980

Ser Gln Asn Thr Thr Ile Ser Ser Leu Ser Glu Lys Ser Lys Glu 1985 1990 1995 Ser Gln Asn Thr Thr Ile Ser Ser Leu Ser Glu Lys Ser Lys Glu 1985 1990 1995

Glu Thr Gly Ile Ser Leu Gln Asp Leu Leu Leu Glu Ile Tyr Arg 2000 2005 2010 Glu Thr Gly Ile Ser Leu Gln Asp Leu Leu Leu Glu Ile Tyr Arg 2000 2005 2010

Ser Ile Gly Glu Pro Asp Ser Leu Tyr Gly Cys Gly Gly Gly Lys 2015 2020 2025 Ser Ile Gly Glu Pro Asp Ser Leu Tyr Gly Cys Gly Gly Gly Lys 2015 2020 2025

Met Leu Gln Pro Ile Thr Arg Leu Arg Thr Tyr Glu His Glu Ala 2030 2035 2040 Met Leu Gln Pro Ile Thr Arg Leu Arg Thr Tyr Glu His Glu Ala 2030 2035 2040

Met Trp Gly Lys Ala Leu Val Thr Tyr Asp Leu Glu Thr Ala Ile Met Trp Gly Lys Ala Leu Val Thr Tyr Asp Leu Glu Thr Ile Wing

2045 2050 2045 2050

Pro Ser Ser Thr Arg Gln Ala Gly Ile Ile Gln Ala Leu Gln Asn 2060 2065 2070 Pro Ser Ser Thr Arg Gln Wing Gly Ile Ile Gln Wing Leu Gln Asn 2060 2065 2070

Leu Gly Leu Cys His Ile Leu Ser Val Tyr Leu Lys Gly Leu Asp 2075 2080 2085 Leu Gly Leu Cys His Ile Leu Ser Val Tyr Leu Lys Gly Leu Asp 2075 2080 2085

Tyr Glu Asn Lys Asp Trp Cys Pro Glu Leu Glu Glu Leu His Tyr 2090 2095 2100 Tyr Glu Asn Lys Asp Trp Cys Pro Glu Leu Glu Glu Leu His Tyr 2090 2095 2100

Gln Ala Ala Trp Arg Asn Met Gln Trp Asp His Cys Thr Ser Val 2105 2110 2115 Gln Wing Wing Trp Arg Asn Met Gln Trp Asp His Cys Thr Ser Val 2105 2110 2115

Ser Lys Glu Val Glu Gly Thr Ser Tyr His Glu Ser Leu Tyr Asn 2120 2125 2130 Ser Lys Glu Val Glu Gly Thr Ser Tyr His Glu Ser Leu Tyr Asn 2120 2125 2130

Ala Leu Gln Ser Leu Arg Asp Arg Glu Phe Ser Thr Phe Tyr Glu 2135 2140 2145 Wing Leu Gln Ser Leu Arg Asp Arg Glu Phe Ser Thr Phe Tyr Glu 2135 2140 2145

Ser Leu Lys Tyr Ala Arg Val Lys Glu Val Glu Glu Met Cys Lys 2150 2155 2160 Ser Leu Lys Tyr Ala Arg Val Lys Glu Val Glu Glu Met Cys Lys 2150 2155 2160

Arg Ser Leu Glu Ser Val Tyr Ser Leu Tyr Pro Thr Leu Ser Arg 2165 2170 2175 Arg Ser Leu Glu Ser Val Tyr Ser Leu Tyr Pro Thr Leu Ser Arg 2165 2170 2175

Leu Gln Ala Ile Gly Glu Leu Glu Ser Ile Gly Glu Leu Phe Ser 2180 2185 2190 Leu Gln Wing Ile Gly Glu Leu Glu Ser Ile Gly Glu Leu Phe Ser 2180 2185 2190

Arg Ser Val Thr His Arg Gln Leu Ser Glu Val Tyr Ile Lys Trp 2195 2200 2205 Arg Ser Val Thr His Arg Gln Leu Ser Glu Val Tyr Ile Lys Trp 2195 2200 2205

Gln Lys His Ser Gln Leu Leu Lys Asp Ser Asp Phe Ser Phe Gln 2210 2215 2220 Gln Lys His Ser Gln Leu Leu Lys Asp Ser Asp Phe Ser Phe Gln 2210 2215 2220

Glu Pro Ile Met Ala Leu Arg Thr Val Ile Leu Glu Ile Leu Met 2225 2230 2235 Glu Pro Ile Met Wing Leu Arg Thr Val Ile Leu Glu Ile Leu Met 2225 2230 2235

Glu Lys Glu Met Asp Asn Ser Gln Arg Glu Cys Ile Lys Asp Ile 2240 2245 2250 Glu Lys Glu Met Asp Asn Ser Gln Arg Glu Cys Ile Lys Asp Ile 2240 2245 2250

Leu Thr Lys His Leu Val Glu Leu Ser Ile Leu Ala Arg Thr Phe 2255 2260 2265 Leu Thr Lys His Leu Val Glu Leu Ser Ile Leu Ala Arg Thr Phe 2255 2260 2265

Lys Asn Thr Gln Leu Pro Glu Arg Ala Ile Phe Gln Ile Lys Gln 2270 2275 2280 Lys Asn Thr Gln Leu Pro Glu Arg Ile Phe Gln Ile Lys Gln 2270 2275 2280

Tyr Asn Ser Val Ser Cys Gly Val Ser Glu Trp Gln Leu Glu Glu 2285 2290 2295 Tyr Asn Ser Val Ser Cys Gly Val Ser Glu Trp Gln Leu Glu Glu 2285 2290 2295

Ala Gln Val Phe Trp Ala Lys Lys Glu Gln Ser Leu Ala Leu Ser 2300 2305 2310 Wing Gln Val Phe Trp Wing Lys Lys Glu Gln Ser Leu Wing Leu Ser 2300 2305 2310

Ile Leu Lys Gln Met Ile Lys Lys Leu Asp Ala Ser Cys Ala Ala 2315 2320 2325 Ile Leu Lys Gln Met Ile Lys Lys Leu Asp Wing Ser Cys Wing Wing 2315 2320 2325

Asn Asn Pro Ser Leu Lys Leu Thr Tyr Thr Glu Cys Leu Arg Val 2330 2335 2340 Asn Asn Pro Ser Leu Lys Leu Thr Tyr Thr Glu Cys Leu Arg Val 2330 2335 2340

Cys Gly Asn Trp Leu Ala Glu Thr Cys Leu Glu Asn Pro Ala Val 2345 2350 2355 Cys Gly Asn Trp Leu Wing Glu Thr Cys Leu Glu Asn Pro Ala Val 2345 2350 2355

Ile Met Gln Thr Tyr Leu Glu Lys Ala Val Glu Val Ala Gly Asn 2360 2365 2370 Ile Met Gln Thr Tyr Leu Glu Lys Wing Val Glu Val Wing Gly Asn 2360 2365 2370

Tyr Asp Gly Glu Ser Ser Asp Glu Leu Arg Asn Gly Lys Met Lys 2375 2380 2385 Ala Phe Leu Ser Leu Ala Arg Phe Ser Asp Thr Gln Tyr Gln Arg 2390 2395 2400 Tyr Asp Gly Glu Ser Be Asp Glu Leu Arg Asn Gly Lys Met Lys 2375 2380 2385 Ala Phe Leu Ser Leu Ala Arg Phe Ser Asp Thr Gln Tyr Gln Arg 2390 2395 2400

Ile Glu Asn Tyr Met Lys Ser Ser Glu Phe Glu Asn Lys Gln Ala 2405 2410 2415 Ile Glu Asn Tyr Met Lys Ser Ser Glu Phe Glu Asn Lys Gln Ala 2405 2410 2415

Leu Leu Lys Arg Ala Lys Glu Glu Val Gly Leu Leu Arg Glu His 2420 2425 2430 Leu Leu Lys Arg Ala Lys Glu Glu Val Gly Leu Leu Arg Glu His 2420 2425 2430

Lys Ile Gln Thr Asn Arg Tyr Thr Val Lys Val Gln Arg Glu Leu 2435 2440 2445 Lys Ile Gln Thr Asn Arg Tyr Thr Val Lys Val Gln Arg Glu Leu 2435 2440 2445

Glu Leu Asp Glu Leu Ala Leu Arg Ala Leu Lys Glu Asp Arg Lys 2450 2455 2460 Glu Leu Asp Glu Leu Ala Leu Arg Ala Leu Lys Glu Asp Arg Lys 2450 2455 2460

Arg Phe Leu Cys Lys Ala Val Glu Asn Tyr Ile Asn Cys Leu Leu 2465 2470 2475 Arg Phe Leu Cys Lys Ala Val Glu Asn Tyr Ile Asn Cys Leu Leu 2465 2470 2475

Ser Gly Glu Glu His Asp Met Trp Val Phe Arg Leu Cys Ser Leu 2480 2485 2490 Ser Gly Glu Glu His Asp Met Trp Val Phe Arg Leu Cys Ser Leu 2480 2485 2490

Trp Leu Glu Asn Ser Gly Val Ser Glu Val Asn Gly Met Met Lys 2495 2500 2505 Trp Leu Glu Asn Ser Gly Val Ser Glu Val Asn Gly Met Met Lys 2495 2500 2505

Ala Asn Gly Met Lys Ile Pro Thr Tyr Lys Phe Leu Pro Leu Met 2510 2515 2520 Wing Asn Gly Met Lys Ile Pro Thr Tyr Lys Phe Leu Pro Leu Met 2510 2515 2520

Tyr Gln Leu Ala Ala Arg Met Gly Thr Lys Met Met Gly Gly Leu 2525 2530 2535 Tyr Gln Leu Wing Wing Arg Met Gly Thr Lys Met Met Gly Gly Leu 2525 2530 2535

Gly Phe His Glu Val Leu Asn Asn Leu Ile Ser Arg Ile Ser Met 2540 2545 2550 Gly Phe His Glu Val Leu Asn Asn Leu Ile Ser Arg Ile Ser Met 2540 2545 2550

Asp His Pro His His Thr Leu Phe Ile Ile Leu Ala Leu Ala Asn 2555 2560 2565 Asp His Pro His His Thr Leu Phe Ile Ile Leu Ala Leu Ala Asn 2555 2560 2565

Ala Asn Arg Asp Glu Phe Leu Thr Lys Pro Glu Val Ala Arg Arg 2570 2575 2580 Wing Asn Arg Asp Glu Phe Leu Thr Lys Pro Glu Val Wing Arg Arg 2570 2575 2580

Ser Arg Ile Thr Lys Asn Val Pro Lys Gln Ser Ser Gln Leu Asp 2585 2590 2595 Ser Arg Ile Thr Lys Asn Val Pro Lys Gln Ser Ser Gln Leu Asp 2585 2590 2595

Glu Asp Arg Thr Glu Ala Ala Asn Arg Ile Ile Cys Thr Ile Arg 2600 2605 2610 Glu Asp Arg Thr Glu Wing Asn Arg Ile Ile Cys Thr Ile Arg 2600 2605 2610

Ser Arg Arg Pro Gln Met Val Arg Ser Val Glu Ala Leu Cys Asp 2615 2620 2625 Ser Arg Arg Pro Gln Met Val Arg Ser Val Glu Ala Leu Cys Asp 2615 2620 2625

Ala Tyr Ile Ile Leu Ala Asn Leu Asp Ala Thr Gln Trp Lys Thr 2630 2635 2640 Wing Tyr Ile Ile Leu Wing Asn Leu Asp Wing Thr Gln Trp Lys Thr 2630 2635 2640

Gln Arg Lys Gly Ile Asn Ile Pro Ala Asp Gln Pro Ile Thr Lys 2645 2650 2655 Gln Arg Lys Gly Ile Asn Ile Pro Wing Asp Gln Pro Ile Thr Lys 2645 2650 2655

Leu Lys Asn Leu Glu Asp Val Val Val Pro Thr Met Glu Ile Lys 2660 2665 2670 Leu Lys Asn Leu Glu Asp Val Val Val Pro Thr Met Glu Ile Lys 2660 2665 2670

Val Asp His Thr Gly Glu Tyr Gly Asn Leu Val Thr Ile Gln Ser 2675 2680 2685 Val Asp His Thr Gly Glu Tyr Gly Asn Leu Val Thr Ile Gln Ser 2675 2680 2685

Phe Lys Ala Glu Phe Arg Leu Ala Gly Gly Val Asn Leu Pro Lys 2690 2695 2700 Phe Lys Wing Glu Phe Arg Leu Wing Gly Gly Val Asn Leu Pro Lys 2690 2695 2700

Ile Ile Asp Cys Val Gly Ser Asp Gly Lys Glu Arg Arg Gln Leu 2705 2710 2715 Ile Ile Asp Cys Val Gly Ser Asp Gly Lys Glu Arg Arg Gln Leu 2705 2710 2715

Val Lys Gly Arg Asp Asp Leu Arg Gln Asp Ala Val Met Gln Gln 2720 2725 2730 Val Phe Gln Met Cys Asn Thr Leu Leu Gln Arg Asn Thr Glu Thr 2735 2740 2745 Val Lys Gly Arg Asp Asp Leu Arg Gln Asp Wing Val Met Gln Gln 2720 2725 2730 Val Phe Gln Met Cys Asn Thr Leu Leu Gln Arg Asn Thr Glu Thr 2735 2740 2745

Arg Lys Arg Lys Leu Thr Ile Cys Thr Tyr Lys Val Val Pro Leu 2750 2755 2760 Arg Lys Arg Lys Leu Thr Ile Cys Thr Tyr Lys Val Val Pro Leu 2750 2755 2760

Ser Gln Arg Ser Gly Val Leu Glu Trp Cys Thr Gly Thr Val Pro 2765 2770 2775 Ser Gln Arg Ser Gly Val Leu Glu Trp Cys Thr Gly Thr Val Pro 2765 2770 2775

Ile Gly Glu Phe Leu Val Asn Asn Glu Asp Gly Ala His Lys Arg 2780 2785 2790 Ile Gly Glu Phe Leu Val Asn Asn Glu Asp Gly Ala His Lys Arg 2780 2785 2790

Tyr Arg Pro Asn Asp Phe Ser Ala Phe Gln Cys Gln Lys Lys Met 2795 2800 2805 Tyr Arg Pro Asn Asp Phe Ser Ala Phe Gln Cys Gln Lys Lys Met 2795 2800 2805

Met Glu Val Gln Lys Lys Ser Phe Glu Glu Lys Tyr Glu Val Phe 2810 2815 2820 Met Glu Val Gln Lys Lys Ser Phe Glu Glu Lys Tyr Glu Val Phe 2810 2815 2820

Met Asp Val Cys Gln Asn Phe Gln Pro Val Phe Arg Tyr Phe Cys 2825 2830 2835 Met Asp Val Cys Gln Asn Phe Gln Pro Val Phe Arg Tyr Phe Cys 2825 2830 2835

Met Glu Lys Phe Leu Asp Pro Ala Ile Trp Phe Glu Lys Arg Leu 2840 2845 2850 Met Glu Lys Phe Leu Asp Pro Wing Ile Trp Phe Glu Lys Arg Leu 2840 2845 2850

Ala Tyr Thr Arg Ser Val Ala Thr Ser Ser Ile Val Gly Tyr Ile 2855 2860 2865 Ala Tyr Thr Arg Ser Val Ala Thr Ser Ser Ile Val Gly Tyr Ile 2855 2860 2865

Leu Gly Leu Gly Asp Arg His Val Gln Asn Ile Leu Ile Asn Glu 2870 2875 2880 Leu Gly Leu Gly Asp Arg His Val Gln Asn Ile Leu Ile Asn Glu 2870 2875 2880

Gln Ser Ala Glu Leu Val His Ile Asp Leu Gly Val Ala Phe Glu 2885 2890 2895 Gln Ser Wing Glu Leu Val His Ile Asp Leu Gly Val Wing Phe Glu 2885 2890 2895

Gln Gly Lys Ile Leu Pro Thr Pro Glu Thr Val Pro Phe Arg Leu 2900 2905 2910 Gln Gly Lys Ile Leu Pro Thr Pro Glu Thr Val Pro Phe Arg Leu 2900 2905 2910

Thr Arg Asp Ile Val Asp Gly Met Gly Ile Thr Gly Val Glu Gly 2915 2920 2925 Thr Arg Asp Ile Val Asp Gly Met Gly Ile Thr Gly Val Glu Gly 2915 2920 2925

Val Phe Arg Arg Cys Cys Glu Lys Thr Met Glu Val Met Arg Asn 2930 2935 2940 Val Phe Arg Arg Cys Cys Glu Lys Thr Met Glu Val Met Arg Asn 2930 2935 2940

Ser Gln Glu Thr Leu Leu Thr Ile Val Glu Val Leu Leu Tyr Asp 2945 2950 2955 Ser Gln Glu Thr Leu Leu Thr Ile Val Glu Val Leu Leu Tyr Asp 2945 2950 2955

Pro Leu Phe Asp Trp Thr Met Asn Pro Leu Lys Ala Leu Tyr Leu 2960 2965 2970 Pro Leu Phe Asp Trp Thr Met Asn Pro Leu Lys Ala Leu Tyr Leu 2960 2965 2970

Gln Gln Arg Pro Glu Asp Glu Thr Glu Leu His Pro Thr Leu Asn 2975 2980 2985 Gln Gln Arg Pro Glu Asp Glu Thr Glu Leu His Pro Thr Leu Asn 2975 2980 2985

Ala Asp Asp Gln Glu Cys Lys Arg Asn Leu Ser Asp Ile Asp Gln 2990 2995 3000 Wing Asp Asp Gln Glu Cys Lys Arg Asn Leu Ser Asp Ile Asp Gln 2990 2995 3000

Ser Phe Asn Lys Val Ala Glu Arg Val Leu Met Arg Leu Gln Glu 3005 3010 3015 Ser Phe Asn Lys Val Wing Glu Arg Val Leu Met Arg Leu Gln Glu 3005 3010 3015

Lys Leu Lys Gly Val Glu Glu Gly Thr Val Leu Ser Val Gly Gly 3020 3025 3030 Lys Leu Lys Gly Val Glu Glu Gly Thr Val Leu Ser Val Gly Gly 3020 3025 3030

Gln Val Asn Leu Leu Ile Gln Gln Ala Ile Asp Pro Lys Asn Leu 3035 3040 3045 Gln Val Asn Leu Leu Ile Gln Gln Ile Wing Asp Pro Lys Asn Leu 3035 3040 3045

Ser Arg Leu Phe Pro Gly Trp Lys Ala Trp Val 3050 3055 Ser Arg Leu Phe Pro Gly Trp Lys Wing Trp Val 3050 3055

<210> 41 <210> 41

<211> 2644 <211> 2644

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 41 Met Gly Glu His Gly Leu Glu Leu Ala Ser Met Ile Pro Ala Leu 1 5 10 15 <400> 41 Met Gly Glu His Gly Leu Glu Leu Ala Ser Met Ile Pro Ala Leu 1 5 10 15

Arg Glu Leu Gly Ser Ala Thr Pro Glu Glu Tyr Asn Thr Val Val 20 25 30 Arg Glu Leu Gly Ser Ala Thr Pro Glu Glu Tyr Asn Thr Val Val 20 25 30

Gln Lys Pro Arg Gln Ile Leu Cys Gln Phe Ile Asp Arg Ile Leu 35 40 45 Gln Lys Pro Arg Gln Ile Leu Cys Gln Phe Ile Asp Arg Ile Leu 35 40 45

Thr Asp Val Asn Val Val Ala Val Glu Leu Val Lys Lys Thr Asp 50 55 60 Thr Asp Val Asn Val Val Wing Val Glu Leu Val Lys Lys Thr Asp 50 55 60

Ser Gln Pro Thr Ser Val Met Leu Leu Asp Phe Ile Gln His Ile 65 70 75 Ser Gln Pro Thr Ser Val Met Leu Leu Asp Phe Ile Gln His Ile 65 70 75

Met Lys Ser Ser Pro Leu Met Phe Val Asn Val Ser Gly Ser His 80 85 90 Met Lys Ser Ser Pro Leu Met Phe Val Asn Val Ser Gly Ser His 80 85 90

Glu Ala Lys Gly Ser Cys Ile Glu Phe Ser Asn Trp Ile Ile Thr 95 100 105 Glu Ala Lys Gly Ser Cys Ile Glu Phe Ser Asn Trp Ile Ile Thr 95 100 105

Arg Leu Leu Arg Ile Ala Ala Thr Pro Ser Cys His Leu Leu His 110 115 120 Arg Leu Leu Arg Ile Ala Wing Thr Pro Ser Cys His Leu Leu His 110 115 120

Lys Lys Ile Cys Glu Val Ile Cys Ser Leu Leu Phe Leu Phe Lys 125 130 135 Lys Lys Ile Cys Glu Val Ile Cys Ser Leu Leu Phe Leu Phe Lys 125 130 135

Ser Lys Ser Pro Ala Ile Phe Gly Val Leu Thr Lys Glu Leu Leu 140 145 150 Ser Lys Ser Pro Ile Phe Gly Val Leu Thr Lys Glu Leu Leu 140 145 150

Gln Leu Phe Glu Asp Leu Val Tyr Leu His Arg Arg Asn Val Met 155 160 165 Gln Leu Phe Glu Asp Leu Val Tyr Leu His Arg Arg Asn Val Met 155 160 165

Gly His Ala Val Glu Trp Pro Val Val Met Ser Arg Phe Leu Ser 170 175 180 Gly His Wing Val Glu Trp Pro Val Val Met Ser Arg Phe Leu Ser 170 175 180

Gln Leu Asp Glu His Met Gly Tyr Leu Gln Ser Ala Pro Leu Gln 185 190 195 Gln Leu Asp Glu His Met Gly Tyr Leu Gln Ser Ala Pro Leu Gln 185 190 195

Leu Met Ser Met Gln Asn Leu Glu Phe Ile Glu Val Thr Leu Leu 200 205 210 Leu Met Ser Met Gln Asn Leu Glu Phe Ile Glu Val Thr Leu Leu 200 205 210

Met Val Leu Thr Arg Ile Ile Ala Ile Val Phe Phe Arg Arg Gln 215 220 225 Met Val Leu Thr Arg Ile Ile Ile Val Phe Phe Arg Arg Gln 215 220 225

Glu Leu Leu Leu Trp Gln Ile Gly Cys Val Leu Leu Glu Tyr Gly 230 235 240 Glu Leu Leu Leu Trp Gln Ile Gly Cys Val Leu Leu Glu Tyr Gly 230 235 240

Ser Pro Lys Ile Lys Ser Leu Ala Ile Ser Phe Leu Thr Glu Leu 245 250 255 Be Pro Lys Ile Lys Be Leu Wing Ile Be Phe Leu Thr Glu Leu 245 250 255

Phe Gln Leu Gly Gly Leu Pro Ala Gln Pro Ala Ser Thr Phe Phe 260 265 270 Phe Gln Leu Gly Gly Leu Pro Wing Gln Pro Wing Ser Thr Phe Phe 260 265 270

Ser Ser Phe Leu Glu Leu Leu Lys His Leu Val Glu Met Asp Thr 275 280 285 Ser Ser Phe Leu Glu Leu Leu Lys His Leu Val Glu Met Asp Thr 275 280 285

Asp Gln Leu Lys Leu Tyr Glu Glu Pro Leu Ser Lys Leu Ile Lys 290 295 300 Asp Gln Leu Lys Leu Tyr Glu Glu Pro Leu Ser Lys Leu Ile Lys 290 295 300

Thr Leu Phe Pro Phe Glu Ala Glu Ala Tyr Arg Asn Ile Glu Pro 305 310 315 Val Tyr Leu Asn Met Leu Leu Glu Lys Leu Cys Val Met Phe Glu 320 325 Thr Leu Phe Pro Phe Glu Ala Glu Ala Tyr Arg Asn Ile Glu Pro 305 310 315 Val Tyr Leu Asn Met Leu Leu Glu Lys Leu Cys Val Met Phe Glu 320 325

Asp Gly Val Leu Met Arg Leu Lys Ser Asp Leu Leu Lys Ala Ala 335 340 345 Asp Gly Val Leu Met Arg Leu Lys Be Asp Leu Leu Lys Wing Wing 335 340 345

Leu Cys His Leu Leu Gln Tyr Phe Leu Lys Phe Val Pro Ala Gly 350 355 360 Leu Cys His Leu Leu Gln Tyr Phe Leu Lys Phe Val Pro Wing Gly 350 355 360

Tyr Glu Ser Ala Leu Gln Val Arg Lys Val Tyr Val Arg Asn Ile 365 370 375 Tyr Glu Ser Ala Leu Gln Val Arg Lys Val Tyr Val Arg Asn Ile 365 370 375

Cys Lys Ala Leu Leu Asp Val Leu Gly Ile Glu Val Asp Ala Glu 380 385 390 Cys Lys Ala Leu Leu Asp Val Leu Gly Ile Glu Val Asp Ala Glu 380 385 390

Tyr Leu Leu Gly Pro Leu Tyr Ala Ala Leu Lys Met Glu Ser Met 395 400 405 Tyr Leu Leu Gly Pro Leu Tyr Wing Wing Leu Lys Met Glu Ser Met 395 400 405

Glu Ile Ile Glu Glu Ile Gln Cys Gln Thr Gln Gln Glu Asn Leu 410 415 420 Glu Ile Ile Glu Glu Ile Gln Cys Gln Thr Gln Gln Glu Asn Leu 410 415 420

Ser Ser Asn Ser Asp Gly Ile Ser Pro Lys Arg Arg Arg Leu Ser 425 430 435 Be Be Asn Be Asp Gly Ile Be Pro Lys Arg Arg Arg Leu Ser 425 430 435

Ser Ser Leu Asn Pro Ser Lys Arg Ala Pro Lys Gln Thr Glu Glu 440 445 450 Ser Ser Leu Asn Pro Ser Lys Arg Ala Pro Lys Gln Thr Glu Glu 440 445 450

Ile Lys His Val Asp Met Asn Gln Lys Ser Ile Leu Trp Ser Ala 455 460 465 Ile Lys His Val Asp Met Asn Gln Lys Ser Ile Leu Trp Ser Ala 455 460 465

Leu Lys Gln Lys Ala Glu Ser Leu Gln Ile Ser Leu Glu Tyr Ser 470 475 480 Leu Lys Gln Lys Wing Glu Ser Leu Gln Ile Ser Leu Glu Tyr Ser 470 475 480

Gly Leu Lys Asn Pro Val Ile Glu Met Leu Glu Gly Ile Ala Val 485 490 495 Gly Leu Lys Asn Pro Val Ile Glu Met Leu Glu Gly Ile Ala Val 485 490 495

Val Leu Gln Leu Thr Ala Leu Cys Thr Val His Cys Ser His Gln 500 505 510 Val Leu Gln Leu Thr Ala Leu Cys Thr Val His Cys Ser His Gln 500 505 510

Asn Met Asn Cys Arg Thr Phe Lys Asp Cys Gln His Lys Ser Lys 515 520 525 Asn Met Asn Cys Arg Thr Phe Lys Asp Cys Gln His Lys Ser Lys 515 520 525

Lys Lys Pro Ser Val Val Ile Thr Trp Met Ser Leu Asp Phe Tyr 530 535 540 Lys Lys Pro Ser Val Val Ile Thr Trp Met Ser Leu Asp Phe Tyr 530 535 540

Thr Lys Val Leu Lys Ser Cys Arg Ser Leu Leu Glu Ser Val Gln 545 550 555 Thr Lys Val Leu Lys Ser Cys Arg Ser Leu Leu Glu Ser Val Gln 545 550 555

Lys Leu Asp Leu Glu Ala Thr Ile Asp Lys Val Val Lys Ile Tyr 560 565 570 Lys Leu Asp Leu Glu Ala Thr Ile Asp Lys Val Val Lys Ile Tyr 560 565 570

Asp Ala Leu Ile Tyr Met Gln Val Asn Ser Ser Phe Glu Asp His 575 580 585 Asp Ala Leu Ile Tyr Met Gln Val Asn Ser Ser Phe Glu Asp His 575 580 585

Ile Leu Glu Asp Leu Cys Gly Met Leu Ser Leu Pro Trp Ile Tyr 590 595 600 Ile Leu Glu Asp Leu Cys Gly Met Leu Ser Leu Pro Trp Ile Tyr 590 595 600

Ser His Ser Asp Asp Gly Cys Leu Lys Leu Thr Thr Phe Ala Ala 605 610 615 Be His Be Asp Asp Gly Cys Leu Lys Leu Thr Thr Phe Wing Wing 605 610 615

Asn Leu Leu Thr Leu Ser Cys Arg Ile Ser Asp Ser Tyr Ser Pro 620 625 630 Asn Leu Leu Thr Leu Ser Cys Arg Ile Ser Asp Ser Tyr Ser Pro 620 625 630

Gln Ala Gln Ser Arg Cys Val Phe Leu Leu Thr Leu Phe Pro Arg 635 640 645 Gln Wing Gln Ser Arg Cys Val Phe Leu Leu Thr Leu Phe Pro Arg 635 640 645

Arg Ile Phe Leu Glu Trp Arg Thr Ala Val Tyr Asn Trp Ala Leu 650 655 Arg Ile Phe Leu Glu Trp Arg Thr Wing Val Tyr Asn Trp Wing Leu 650 655

Gln Ser Ser His Glu Val Ile Arg Ala Ser Cys Val Ser Gly Phe 665 670 Gln Ser Be His Glu Val Ile Arg Ala Ser Cys Val Ser Gly Phe 665 670

Phe Ile Leu Leu Gln Gln Gln Asn Ser Cys Asn Arg Val Pro Lys 680 685 690 Phe Ile Leu Leu Gln Gln Gln Asn Ser Cys Asn Arg Val Pro Lys 680 685 690

Ile Leu Ile Asp Lys Val Lys Asp Asp Ser Asp Ile Val Lys Lys 695 700 705 Ile Leu Ile Asp Lys Val Lys Asp Asp Ser Asp Ile Val Lys Lys 695 700 705

Glu Phe Ala Ser Ile Leu Gly Gln Leu Val Cys Thr Leu His Gly 710 715 720 Glu Phe Ala Ser Ile Leu Gly Gln Leu Val Cys Thr Leu His Gly 710 715 720

Met Phe Tyr Leu Thr Ser Ser Leu Thr Glu Pro Phe Ser Glu His 725 730 735 Met Phe Tyr Leu Thr Ser Ser Leu Thr Glu Pro Phe Ser Glu His 725 730 735

Gly His Val Asp Leu Phe Cys Arg Asn Leu Lys Ala Thr Ser Gln 740 745 750 Gly His Val Asp Leu Phe Cys Arg Asn Leu Lys Ala Thr Ser Gln 740 745 750

His Glu Cys Ser Ser Ser Gln Leu Lys Ala Ser Val Cys Lys Pro 755 760 765 His Glu Cys Ser Ser Ser Gln Leu Lys Ala Ser Val Cys Lys Pro 755 760 765

Phe Leu Phe Leu Leu Lys Lys Lys Ile Pro Ser Pro Val Lys Leu 770 775 780 Phe Leu Phe Leu Leu Lys Lys Lys Ile Pro Ser Pro Val Lys Leu 770 775 780

Ala Phe Ile Asp Asn Leu His His Leu Cys Lys His Leu Asp Phe 785 790 795 Ala Phe Ile Asp Asn Leu His His Leu Cys Lys His Leu Asp Phe 785 790 795

Arg Glu Asp Glu Thr Asp Val Lys Ala Val Leu Gly Thr Leu Leu 800 805 810 Arg Glu Asp Glu Thr Asp Val Lys Wing Val Leu Gly Thr Leu Leu 800 805 810

Asn Leu Met Glu Asp Pro Asp Lys Asp Val Arg Val Ala Phe Ser 815 820 825 Asn Leu Met Glu Asp Pro Asp Lys Asp Val Arg Val Ala Phe Ser 815 820 825

Gly Asn Ile Lys His Ile Leu Glu Ser Leu Asp Ser Glu Asp Gly 830 835 840 Gly Asn Ile Lys His Ile Leu Glu Ser Leu Asp Ser Glu Asp Gly 830 835 840

Phe Ile Lys Glu Leu Phe Val Leu Arg Met Lys Glu Ala Tyr Thr 845 850 855 Phe Ile Lys Glu Leu Phe Val Leu Arg Met Lys Glu Ala Tyr Thr 845 850 855

His Ala Gln Ile Ser Arg Asn Asn Glu Leu Lys Asp Thr Leu Ile 860 865 870 His Wing Gln Ile Ser Arg Asn Asn Glu Leu Lys Asp Thr Leu Ile 860 865 870

Leu Thr Thr Gly Asp Ile Gly Arg Ala Ala Lys Gly Asp Leu Val 875 880 885 Leu Thr Thr Gly Asp Ile Gly Arg Wing Wing Lys Gly Asp Leu Val 875 880 885

Pro Phe Ala Leu Leu His Leu Leu His Cys Leu Leu Ser Lys Ser 890 895 900 Pro Phe Ala Leu Leu His Leu Leu His Cys Leu Leu Ser Lys Ser 890 895 900

Ala Ser Val Ser Gly Ala Ala Tyr Thr Glu Ile Arg Ala Leu Val 905 910 915 Wing Ser Val Ser Gly Wing Wing Tyr Thr Glu Ile Arg Wing Leu Val 905 910 915

Ala Ala Lys Ser Val Lys Leu Gln Ser Phe Phe Ser Gln Tyr Lys 920 925 930 Wing Wing Lys Ser Val Lys Leu Gln Ser Phe Phe Ser Gln Tyr Lys 920 925 930

Lys Pro Ile Cys Gln Phe Leu Val Glu Ser Leu His Ser Ser Gln 935 940 945 Lys Pro Ile Cys Gln Phe Leu Val Glu Ser Leu His Ser Ser Gln 935 940 945

Met Thr Ala Leu Pro Asn Thr Pro Cys Gln Asn Ala Asp Val Arg 950 955 960 Met Thr Wing Leu Pro Asn Thr Pro Cys Gln Asn Wing Asp Val Arg 950 955 960

Lys Gln Asp Val Ala His Gln Arg Glu Met Ala Leu Asn Thr Leu 965 970 975 Lys Gln Asp Val Wing His Gln Arg Glu Met Wing Leu Asn Thr Leu 965 970 975

Ser Glu Ile Ala Asn Val Phe Asp Phe Pro Asp Leu Asn Arg Phe 980 985 990 Ser Glu Ile Wing Asn Val Phe Asp Phe Pro Asp Leu Asn Arg Phe 980 985 990

Leu Thr Arg Thr Leu Gln Val Leu Leu Pro Asp Leu Ala Ala Lys Leu Thr Arg Thr Leu Gln Val Leu Leu Pro Asp Leu Wing Wing Lys

995 1000 995 1000

Ala Ser Pro Ala Ala Ser Ala Leu Ile Arg Thr Leu Gly Lys Gln 1010 1015 1020 Ala Ser Pro Ala Ala Ser Ala Leu Ile Arg Thr Leu Gly Lys Gln 1010 1015 1020

Leu Asn Val Asn Arg Arg Glu Ile Leu Ile Asn Asn Phe Lys Tyr 1025 1030 1035 Leu Asn Val Asn Arg Arg Glu Ile Leu Ile Asn Asn Phe Lys Tyr 1025 1030 1035

Ile Phe Ser His Leu Val Cys Ser Cys Ser Lys Asp Glu Leu Glu 1040 1045 1050 Ile Phe Ser His Leu Val Cys Ser Cys Ser Lys Asp Glu Leu Glu 1040 1045 1050

Arg Ala Leu His Tyr Leu Lys Asn Glu Thr Glu Ile Glu Leu Gly 1055 1060 1065 Arg Ala Leu His Tyr Leu Lys Asn Glu Thr Glu Ile Glu Leu Gly 1055 1060 1065

Ser Leu Leu Arg Gln Asp Phe Gln Gly Leu His Asn Glu Leu Leu 1070 1075 1080 Ser Leu Leu Arg Gln Asp Phe Gln Gly Leu His Asn Glu Leu Leu 1070 1075 1080

Leu Arg Ile Gly Glu His Tyr Gln Gln Val Phe Asn Gly Leu Ser 1085 1090 1095 Leu Arg Ile Gly Glu His Tyr Gln Gln Val Phe Asn Gly Leu Ser 1085 1090 1095

Ile Leu Ala Ser Phe Ala Ser Ser Asp Asp Pro Tyr Gln Gly Pro 1100 1105 1110 Ile Leu Ala Be Phe Ala Be Be Asp Asp Pro Tyr Gln Gly Pro 1100 1105 1110

Arg Asp Ile Ile Ser Pro Glu Leu Met Ala Asp Tyr Leu Gln Pro 1115 1120 1125 Arg Asp Ile Ile Ser Pro Glu Leu Met Wing Asp Tyr Leu Gln Pro 1115 1120 1125

Lys Leu Leu Gly Ile Leu Ala Phe Phe Asn Met Gln Leu Leu Ser 1130 1135 1140 Lys Leu Leu Gly Ile Leu Ala Phe Phe Asn Met Gln Leu Leu Ser 1130 1135 1140

Ser Ser Val Gly Ile Glu Asp Lys Lys Met Ala Leu Asn Ser Leu 1145 1150 1155 Ser Ser Val Gly Ile Glu Asp Lys Lys Met Ala Leu Asn Ser Leu 1145 1150 1155

Met Ser Leu Met Lys Leu Met Gly Pro Lys His Val Ser Ser Val 1160 1165 1170 Met Ser Leu Met Lys Leu Met Gly Pro Lys His Val Ser Ser Val 1160 1165 1170

Arg Val Lys Met Met Thr Thr Leu Arg Thr Gly Leu Arg Phe Lys 1175 1180 1185 Arg Val Lys Met Met Thr Thr Leu Arg Thr Gly Leu Arg Phe Lys 1175 1180 1185

Asp Asp Phe Pro Glu Leu Cys Cys Arg Ala Trp Asp Cys Phe Val 1190 1195 1200 Asp Asp Phe Pro Glu Leu Cys Cys Arg Wing Trp Asp Cys Phe Val 1190 1195 1200

Arg Cys Leu Asp His Ala Cys Leu Gly Ser Leu Leu Ser His Val 1205 1210 1215 Arg Cys Leu Asp His Ala Cys Leu Gly Ser Leu Leu Ser His Val 1205 1210 1215

Ile Val Ala Leu Leu Pro Leu Ile His Ile Gln Pro Lys Glu Thr 1220 1225 1230 Ile Val Ala Leu Leu Pro Leu Ile His Ile Gln Pro Lys Glu Thr 1220 1225 1230

Ala Ala Ile Phe His Tyr Leu Ile Ile Glu Asn Arg Asp Ala Val 1235 1240 1245 Wing Wing Ile Phe His Tyr Leu Ile Ile Glu Asn Arg Asp Wing Val 1235 1240 1245

Gln Asp Phe Leu His Glu Ile Tyr Phe Leu Pro Asp His Pro Glu 1250 1255 1260 Gln Asp Phe Leu His Glu Ile Tyr Phe Leu Pro Asp His Pro Glu 1250 1255 1260

Leu Lys Lys Ile Lys Ala Val Leu Gln Glu Tyr Arg Lys Glu Thr 1265 1270 1275 Leu Lys Lys Ile Lys Ala Val Leu Gln Glu Tyr Arg Lys Glu Thr 1265 1270 1275

Ser Glu Ser Thr Asp Leu Gln Thr Thr Leu Gln Leu Ser Met Lys 1280 1285 1290 Ser Glu Ser Thr Asp Leu Gln Thr Thr Leu Gln Leu Ser Met Lys 1280 1285 1290

Ala Ile Gln His Glu Asn Val Asp Val Arg Ile His Ala Leu Thr 1295 1300 1305 Ile Gln His Glu Asn Val Asp Val Arg Ile His Wing Leu Thr 1295 1300 1305

Ser Leu Lys Glu Thr Leu Tyr Lys Asn Gln Glu Lys Leu Ile Lys 1310 1315 1320 Ser Leu Lys Glu Thr Leu Tyr Lys Asn Gln Glu Lys Leu Ile Lys 1310 1315 1320

Tyr Ala Thr Asp Ser Glu Thr Val Glu Pro Ile Ile Ser Gln Leu 1325 1330 1335 Val Thr Val Leu Leu Lys Gly Cys Gln Asp Ala Asn Ser Gln Ala 1340 1345 1350 Tyr Ala Thr Asp Ser Glu Thr Val Glu Pro Ile Ile Ser Gln Leu 1325 1330 1335 Val Thr Val Leu Leu Lys Gly Cys Gln Asp Ala Asn Ser Gln Ala 1340 1345 1350

Arg Leu Leu Cys Gly Glu Cys Leu Gly Glu Leu Gly Ala Ile Asp 1355 1360 1365 Arg Leu Leu Cys Gly Glu Cys Leu Gly Glu Leu Gly Ala Ile Asp 1355 1360 1365

Pro Gly Arg Leu Asp Phe Ser Thr Thr Glu Thr Gln Gly Lys Asp 1370 1375 1380 Pro Gly Arg Leu Asp Phe Ser Thr Thr Glu Thr Gln Gly Lys Asp 1370 1375 1380

Phe Thr Phe Val Thr Gly Val Glu Asp Ser Ser Phe Ala Tyr Gly 1385 1390 1395 Phe Thr Phe Val Thr Gly Val Glu Asp Ser Ser Phe Ala Tyr Gly 1385 1390 1395

Leu Leu Met Glu Leu Thr Arg Ala Tyr Leu Ala Tyr Ala Asp Asn 1400 1405 1410 Leu Leu Met Glu Leu Thr Arg Wing Tyr Leu Wing Tyr Wing Asp Asn 1400 1405 1410

Ser Arg Ala Gln Asp Ser Ala Ala Tyr Ala Ile Gln Glu Leu Leu 1415 1420 1425 Be Arg Wing Gln Asp Be Wing Tyr Wing Ile Gln Glu Leu Leu 1415 1420 1425

Ser Ile Tyr Asp Cys Arg Glu Met Glu Thr Asn Gly Pro Gly His 1430 1435 1440 Ser Ile Tyr Asp Cys Arg Glu Met Glu Thr Asn Gly Pro Gly His 1430 1435 1440

Gln Leu Trp Arg Arg Phe Pro Glu His Val Arg Glu Ile Leu Glu 1445 1450 1455 Gln Leu Trp Arg Arg Phe Pro Glu His Val Arg Glu Ile Leu Glu 1445 1450 1455

Pro His Leu Asn Thr Arg Tyr Lys Ser Ser Gln Lys Ser Thr Asp 1460 1465 1470 Pro His Leu Asn Thr Arg Tyr Lys Ser Ser Gln Lys Ser Thr Asp 1460 1465 1470

Trp Ser Gly Val Lys Lys Pro Ile Tyr Leu Ser Lys Leu Gly Ser 1475 1480 1485 Trp Ser Gly Val Lys Lys Pro Ile Tyr Leu Ser Lys Leu Gly Ser 1475 1480 1485

Asn Phe Ala Glu Trp Ser Ala Ser Trp Ala Gly Tyr Leu Ile Thr 1490 1495 1500 Asn Phe Ala Glu Trp Ser Ala Ser Trp Ala Gly Tyr Leu Ile Thr 1490 1495 1500

Lys Val Arg His Asp Leu Ala Ser Lys Ile Phe Thr Cys Cys Ser 1505 1510 1515 Lys Val Arg His Asp Leu Ala Ser Lys Ile Phe Thr Cys Cys Ser 1505 1510 1515

Ile Met Met Lys His Asp Phe Lys Val Thr Ile Tyr Leu Leu Pro 1520 1525 1530 Ile Met Met Lys His Asp Phe Lys Val Thr Ile Tyr Leu Leu Pro 1520 1525 1530

His Ile Leu Val Tyr Val Leu Leu Gly Cys Asn Gln Glu Asp Gln 1535 1540 1545 His Ile Leu Val Tyr Val Leu Leu Gly Cys Asn Gln Glu Asp Gln 1535 1540 1545

Gln Glu Val Tyr Ala Glu Ile Met Ala Val Leu Lys His Asp Asp 1550 1555 1560 Gln Glu Val Tyr Ala Glu Ile Met Ala Val Leu Lys His Asp Asp 1550 1555 1560

Gln His Thr Ile Asn Thr Gln Asp Ile Ala Ser Asp Leu Cys Gln 1565 1570 1575 Gln His Thr Ile Asn Thr Gln Asp Ile Ala Ser Asp Leu Cys Gln 1565 1570 1575

Leu Ser Thr Gln Thr Val Phe Ser Met Leu Asp His Leu Thr Gln 1580 1585 1590 Leu Ser Thr Gln Thr Val Phe Ser Met Leu Asp His Leu Thr Gln 1580 1585 1590

Trp Ala Arg His Lys Phe Gln Ala Leu Lys Ala Glu Lys Cys Pro 1595 1600 1605 Trp Wing Arg His Lys Phe Gln Wing Leu Lys Wing Glu Lys Cys Pro 1595 1600 1605

His Ser Lys Ser Asn Arg Asn Lys Val Asp Ser Met Val Ser Thr 1610 1615 1620 His Ser Lys Ser Asn Arg Asn Lys Val Asp Ser Met Val Ser Thr 1610 1615 1620

Val Asp Tyr Glu Asp Tyr Gln Ser Val Thr Arg Phe Leu Asp Leu 1625 1630 1635 Val Asp Tyr Glu Asp Tyr Gln Ser Val Thr Arg Phe Leu Asp Leu 1625 1630 1635

Ile Pro Gln Asp Thr Leu Ala Val Ala Ser Phe Arg Ser Lys Ala 1640 1645 1650 Ile Pro Gln Asp Thr Leu Wing Val Wing Ser Phe Arg Ser Lys Wing 1640 1645 1650

Tyr Thr Arg Ala Val Met His Phe Glu Ser Phe Ile Thr Glu Lys 1655 1660 1665 Tyr Thr Arg Ala Val Met His Phe Glu Ser Phe Ile Thr Glu Lys 1655 1660 1665

Lys Gln Asn Ile Gln Glu His Leu Gly Phe Leu Gln Lys Leu Tyr 1670 1675 1680 Ala Ala Met His Glu Pro Asp Gly Val Ala Gly Val Ser Ala Ile 1685 1690 1695 Lys Gln Asn Ile Gln Glu His Leu Gly Phe Leu Gln Lys Leu Tyr 1670 1675 1680 Ala Wing Met His Glu Pro Asp Gly Val Wing Gly Val Ser Wing Ile 1685 1690 1695

Arg Lys Ala Glu Pro Ser Leu Lys Glu Gln Ile Leu Glu His Glu 1700 1705 1710 Arg Lys Wing Glu Pro Ser Leu Lys Glu Gln Ile Leu Glu His Glu 1700 1705 1710

Ser Leu Gly Leu Leu Arg Asp Ala Thr Ala Cys Tyr Asp Arg Ala 1715 1720 1725 Ser Leu Gly Leu Leu Arg Asp Wing Thr Wing Cys Tyr Asp Arg Wing 1715 1720 1725

Ile Gln Leu Glu Pro Asp Gln Ile Ile His Tyr His Gly Val Val 1730 1735 1740 Ile Gln Leu Glu Pro Asp Gln Ile Ile His Tyr His Gly Val Val 1730 1735 1740

Lys Ser Met Leu Gly Leu Gly Gln Leu Ser Thr Val Ile Thr Gln 1745 1750 1755 Lys Ser Met Leu Gly Leu Gly Gln Leu Ser Thr Val Ile Thr Gln 1745 1750 1755

Val Asn Gly Val His Ala Asn Arg Ser Glu Trp Thr Asp Glu Leu 1760 1765 1770 Val Asn Gly Val His Ala Asn Arg Ser Glu Trp Thr Asp Glu Leu 1760 1765 1770

Asn Thr Tyr Arg Val Glu Ala Ala Trp Lys Leu Ser Gln Trp Asp 1775 1780 1785 Asn Thr Tyr Arg Val Glu Wing Trp Lys Leu Ser Gln Trp Asp 1775 1780 1785

Leu Val Glu Asn Tyr Leu Ala Ala Asp Gly Lys Ser Thr Thr Trp 1790 1795 1800 Leu Val Glu Asn Tyr Leu Wing Wing Asp Gly Lys Ser Thr Thr Trp 1790 1795 1800

Ser Val Arg Leu Gly Gln Leu Leu Leu Ser Ala Lys Lys Arg Asp 1805 1810 1815 Ser Val Arg Leu Gly Gln Leu Leu Leu Ser Ala Lys Lys Arg Asp 1805 1810 1815

Ile Thr Ala Phe Tyr Asp Ser Leu Lys Leu Val Arg Ala Glu Gln 1820 1825 1830 Ile Thr Ala Phe Tyr Asp Ser Leu Lys Leu Val Arg Ala Glu Gln 1820 1825 1830

Ile Val Pro Leu Ser Ala Ala Ser Phe Glu Arg Gly Ser Tyr Gln 1835 1840 1845 Ile Val Pro Leu Be Wing Be Ser Phe Glu Arg Gly Ser Tyr Gln 1835 1840 1845

Arg Gly Tyr Glu Tyr Ile Val Arg Leu His Met Leu Cys Glu Leu 1850 1855 1860 Arg Gly Tyr Glu Tyr Ile Val Arg Leu His Met Leu Cys Glu Leu 1850 1855 1860

Glu His Ser Ile Lys Pro Leu Phe Gln His Ser Pro Gly Asp Ser 1865 1870 1875 Glu His Ser Ile Lys Pro Leu Phe Gln His Ser Pro Gly Asp Ser 1865 1870 1875

Ser Gln Glu Asp Ser Leu Asn Trp Val Ala Arg Leu Glu Met Thr 1880 1885 1890 Ser Gln Glu Asp Ser Leu Asn Trp Val Ala Arg Leu Glu Met Thr 1880 1885 1890

Gln Asn Ser Tyr Arg Ala Lys Glu Pro Ile Leu Ala Leu Arg Arg 1895 1900 1905 Gln Asn Ser Tyr Arg Ala Lys Glu Pro Ile Leu Ala Leu Arg Arg 1895 1900 1905

Ala Leu Leu Ser Leu Asn Lys Arg Pro Asp Tyr Asn Glu Met Val 1910 1915 1920 Ala Leu Leu Ser Leu Asn Lys Arg Pro Asp Tyr Asn Glu Met Val 1910 1915 1920

Gly Glu Cys Trp Leu Gln Ser Ala Arg Val Ala Arg Lys Ala Gly 1925 1930 1935 Gly Glu Cys Trp Leu Gln Ser Ala Arg Val Ala Arg Lys Ala Gly 1925 1930 1935

His His Gln Thr Ala Tyr Asn Ala Leu Leu Asn Ala Gly Glu Ser 1940 1945 1950 His His Gln Thr Ala Tyr Asn Ala Leu Leu Asn Ala Gly Glu Ser 1940 1945 1950

Arg Leu Ala Glu Leu Tyr Val Glu Arg Ala Lys Trp Leu Trp Ser 1955 1960 1965 Arg Leu Wing Glu Leu Tyr Val Glu Arg Wing Lys Trp Leu Trp Ser 1955 1960 1965

Lys Gly Asp Val His Gln Ala Leu Ile Val Leu Gln Lys Gly Val 1970 1975 1980 Lys Gly Asp Val His Gln Ala Leu Ile Val Leu Gln Lys Gly Val 1970 1975 1980

Glu Leu Cys Phe Pro Glu Asn Glu Thr Pro Pro Glu Gly Lys Asn 1985 1990 1995 Glu Leu Cys Phe Pro Glu Asn Glu Thr Pro Pro Glu Gly Lys Asn 1985 1990 1995

Met Leu Ile His Gly Arg Ala Met Leu Leu Val Gly Arg Phe Met 2000 2005 2010 Met Leu Ile His Gly Arg Wing Met Leu Leu Val Gly Arg Phe Met 2000 2005 2010

Glu Glu Thr Ala Asn Phe Glu Ser Asn Ala Ile Met Lys Lys Tyr Glu Glu Thr Wing Asn Phe Glu Ser Asn Wing Ile Met Lys Lys Tyr

2015 2020 2015 2020

Lys Asp Val Thr Ala Cys Leu Pro Glu Trp Glu Asp Gly His Phe 2030 2035 2040 Lys Asp Val Thr Ala Cys Leu Pro Glu Trp Glu Asp Gly His Phe 2030 2035 2040

Tyr Leu Ala Lys Tyr Tyr Asp Lys Leu Met Pro Met Val Thr Asp 2045 2050 2055 Tyr Leu Ala Lys Tyr Tyr Asp Lys Leu Met Pro Met Val Thr Asp 2045 2050 2055

Asn Lys Met Glu Lys Gln Gly Asp Leu Ile Arg Tyr Ile Val Leu 2060 2065 2070 Asn Lys Met Glu Lys Gln Gly Asp Leu Ile Arg Tyr Ile Val Leu 2060 2065 2070

His Phe Gly Arg Ser Leu Gln Tyr Gly Asn Gln Phe Ile Tyr Gln 2075 2080 2085 His Phe Gly Arg Ser Leu Gln Tyr Gly Asn Gln Phe Ile Tyr Gln 2075 2080 2085

Ser Met Pro Arg Met Leu Thr Leu Trp Leu Asp Tyr Gly Thr Lys 2090 2095 2100 Ser Met Pro Arg Met Leu Thr Leu Trp Leu Asp Tyr Gly Thr Lys 2090 2095 2100

Ala Tyr Glu Trp Glu Lys Ala Gly Arg Ser Asp Arg Val Gln Met 2105 2110 2115 Wing Tyr Glu Trp Glu Lys Wing Gly Arg Ser Asp Arg Val Gln Met 2105 2110 2115

Arg Asn Asp Leu Gly Lys Ile Asn Lys Val Ile Thr Glu His Thr 2120 2125 2130 Arg Asn Asp Leu Gly Lys Ile Asn Lys Val Ile Thr Glu His Thr 2120 2125 2130

Asn Tyr Leu Ala Pro Tyr Gln Phe Leu Thr Ala Phe Ser Gln Leu 2135 2140 2145 Asn Tyr Leu Wing Pro Tyr Gln Phe Leu Thr Wing Phe Ser Gln Leu 2135 2140 2145

Ile Ser Arg Ile Cys His Ser His Asp Glu Val Phe Val Val Leu 2150 2155 2160 Ile Ser Arg Ile Cys His Ser His Asp Glu Val Phe Val Val Leu 2150 2155 2160

Met Glu Ile Ile Ala Lys Val Phe Leu Ala Tyr Pro Gln Gln Ala 2165 2170 2175 Met Glu Ile Ile Wing Lys Val Phe Leu Wing Tyr Pro Gln Gln Wing 2165 2170 2175

Met Trp Met Met Thr Ala Val Ser Lys Ser Ser Tyr Pro Met Arg 2180 2185 2190 Met Trp Met Met Thr Ala Val Ser Lys Ser Ser Tyr Pro Met Arg 2180 2185 2190

Val Asn Arg Cys Lys Glu Ile Leu Asn Lys Ala Ile His Met Lys 2195 2200 2205 Val Asn Arg Cys Lys Glu Ile Leu Asn Lys Ile Wing His Met Lys 2195 2200 2205

Lys Ser Leu Glu Lys Phe Val Gly Asp Ala Thr Arg Leu Thr Asp 2210 2215 2220 Lys Ser Leu Glu Lys Phe Val Gly Asp Wing Thr Arg Leu Thr Asp 2210 2215 2220

Lys Leu Leu Glu Leu Cys Asn Lys Pro Val Asp Gly Ser Ser Ser 2225 2230 2235 Lys Leu Leu Glu Leu Cys Asn Lys Pro Val Asp Gly Ser Ser Ser 2225 2230 2235

Thr Leu Ser Met Ser Thr His Phe Lys Met Leu Lys Lys Leu Val 2240 2245 2250 Thr Leu Ser Met Ser Thr His Phe Lys Met Leu Lys Lys Leu Val 2240 2245 2250

Glu Glu Ala Thr Phe Ser Glu Ile Leu Ile Pro Leu Gln Ser Val 2255 2260 2265 Glu Glu Ala Thr Phe Ser Glu Ile Leu Ile Pro Leu Gln Ser Val 2255 2260 2265

Met Ile Pro Thr Leu Pro Ser Ile Leu Gly Thr His Ala Asn His 2270 2275 2280 Met Ile Pro Thr Leu Pro Ser Ile Leu Gly Thr His Ala Asn His 2270 2275 2280

Ala Ser His Glu Pro Phe Pro Gly His Trp Ala Tyr Ile Ala Gly 2285 2290 2295 Ala Ser His Glu Pro Phe Pro Gly His Trp Ala Tyr Ile Ala Gly 2285 2290 2295

Phe Asp Asp Met Val Glu Ile Leu Ala Ser Leu Gln Lys Pro Lys 2300 2305 2310 Phe Asp Asp Met Val Glu Ile Leu Ala Ser Leu Gln Lys Pro Lys 2300 2305 2310

Lys Ile Ser Leu Lys Gly Ser Asp Gly Lys Phe Tyr Ile Met Met 2315 2320 2325 Lys Ile Ser Leu Lys Gly Ser Asp Gly Lys Phe Tyr Ile Met Met 2315 2320 2325

Cys Lys Pro Lys Asp Asp Leu Arg Lys Asp Cys Arg Leu Met Glu 2330 2335 2340 Cys Lys Pro Lys Asp Asp Leu Arg Lys Asp Cys Arg Leu Met Glu 2330 2335 2340

Phe Asn Ser Leu Ile Asn Lys Cys Leu Arg Lys Asp Ala Glu Ser 2345 2350 2355 Phe Asn Ser Leu Ile Asn Lys Cys Leu Arg Lys Asp Ala Glu Ser 2345 2350 2355

Arg Arg Arg Glu Leu His Ile Arg Thr Tyr Ala Val Ile Pro Leu 2360 2365 2370 Arg Arg Arg Glu Leu His Ile Arg Thr Tyr Ala Val Ile Pro Leu 2360 2365 2370

Asn Asp Glu Cys Gly Ile Ile Glu Trp Val Asn Asn Thr Ala Gly 2375 2380 2385 Asn Asp Glu Cys Gly Ile Ile Glu Trp Val Asn Asn Thr Wing Gly 2375 2380 2385

Leu Arg Pro Ile Leu Thr Lys Leu Tyr Lys Glu Lys Gly Val Tyr 2390 2395 2400 Leu Arg Pro Ile Leu Thr Lys Leu Tyr Lys Glu Lys Gly Val Tyr 2390 2395 2400

Met Thr Gly Lys Glu Leu Arg Gln Cys Met Leu Pro Lys Ser Ala 2405 2410 2415 Met Thr Gly Lys Glu Leu Arg Gln Cys Met Leu Pro Lys Ser Ala 2405 2410 2415

Ala Leu Ser Glu Lys Leu Lys Val Phe Arg Glu Phe Leu Leu Pro 2420 2425 2430 Wing Leu Ser Glu Lys Leu Lys Val Phe Arg Glu Phe Leu Leu Pro 2420 2425 2430

Arg His Pro Pro Ile Phe His Glu Trp Phe Leu Arg Thr Phe Pro 2435 2440 2445 Arg His Pro Pro Ile Phe His Glu Trp Phe Leu Arg Thr Phe Pro 2435 2440 2445

Asp Pro Thr Ser Trp Tyr Ser Ser Arg Ser Ala Tyr Cys Arg Ser 2450 2455 2460 Asp Pro Thr Ser Trp Tyr Ser Ser Arg Ser Ala Tyr Cys Arg Ser 2450 2455 2460

Thr Ala Val Met Ser Met Val Gly Tyr Ile Leu Gly Leu Gly Asp 2465 2470 2475 Thr Ala Val Met Ser Met Val Gly Tyr Ile Leu Gly Leu Gly Asp 2465 2470 2475

Arg His Gly Glu Asn Ile Leu Phe Asp Ser Leu Thr Gly Glu Cys 2480 2485 2490 Arg His Gly Glu Asn Ile Leu Phe Asp Ser Leu Thr Gly Glu Cys 2480 2485 2490

Val His Val Asp Phe Asn Cys Leu Phe Asn Lys Gly Glu Thr Phe 2495 2500 2505 Val His Val Asp Phe Asn Cys Leu Phe Asn Lys Gly Glu Thr Phe 2495 2500 2505

Glu Val Pro Glu Ile Val Pro Phe Arg Leu Thr His Asn Met Val 2510 2515 2520 Glu Val Pro Glu Ile Val Pro Phe Arg Leu Thr His Asn Met Val 2510 2515 2520

Asn Gly Met Gly Pro Met Gly Thr Glu Gly Leu Phe Arg Arg Ala 2525 2530 2535 Asn Gly Met Gly Pro Met Gly Thr Glu Gly Leu Phe Arg Arg Ala 2525 2530 2535

Cys Glu Val Thr Met Arg Leu Met Arg Asp Gln Arg Glu Pro Leu 2540 2545 2550 Cys Glu Val Thr Met Arg Leu Met Arg Asp Gln Arg Glu Pro Leu 2540 2545 2550

Met Ser Val Leu Lys Thr Phe Leu His Asp Pro Leu Val Glu Trp 2555 2560 2565 Met Ser Val Leu Lys Thr Phe Leu His Asp Pro Leu Val Glu Trp 2555 2560 2565

Ser Lys Pro Val Lys Gly His Ser Lys Ala Pro Leu Asn Glu Thr 2570 2575 2580 Ser Lys Pro Val Lys Gly His Ser Lys Ala Pro Leu Asn Glu Thr 2570 2575 2580

Gly Glu Val Val Asn Glu Lys Ala Lys Thr His Val Leu Asp Ile 2585 2590 2595 Gly Glu Val Val Asn Glu Lys Ala Lys Thr His Val Leu Asp Ile 2585 2590 2595

Glu Gln Arg Leu Gln Gly Val Ile Lys Thr Arg Asn Arg Val Thr 2600 2605 2610 Glu Gln Arg Leu Gln Gly Val Ile Lys Thr Arg Asn Arg Val Thr 2600 2605 2610

Gly Leu Pro Leu Ser Ile Glu Gly His Val His Tyr Leu Ile Gln 2615 2620 2625 Gly Leu Pro Leu Ser Ile Glu Gly His Val His Tyr Leu Ile Gln 2615 2620 2625

Glu Ala Thr Asp Glu Asn Leu Leu Cys Gln Met Tyr Leu Gly Trp 2630 2635 2640 Glu Ala Thr Asp Glu Asn Leu Leu Cys Gln Met Tyr Leu Gly Trp 2630 2635 2640

Thr Pro Tyr Met Thr Pro Tyr Met

<210> 42 <210> 42

<211> 627 <211> 627

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 42 Met Cys Val Pro Arg Ser Gly Leu Ile Leu Ser Cys Ile Cys Leu 1 5 10 15 <400> 42 Met Cys Val Pro Arg Ser Gly Leu Ile Leu Ser Cys Ile Cys Leu 1 5 10 15

Tyr Cys Gly Val Leu Leu Pro Val Leu Leu Pro Asn Leu Pro Phe 20 25 Tyr Cys Gly Val Leu Leu Pro Val Leu Leu Pro Asn Leu Pro Phe 20 25

Leu Thr Cys Leu Ser Met Ser Thr Leu Glu Ser Val Thr Tyr Leu 35 40 45 Leu Thr Cys Leu Ser Met Ser Thr Leu Glu Ser Val Thr Tyr Leu 35 40 45

Pro Glu Lys Gly Leu Tyr Cys Gln Arg Leu Pro Ser Ser Arg Thr 50 55 60 Pro Glu Lys Gly Leu Tyr Cys Gln Arg Leu Pro Ser Ser Arg Thr 50 55 60

His Gly Gly Thr Glu Ser Leu Lys Gly Lys Asn Thr Glu Asn Met 65 70 75 His Gly Gly Thr Glu Ser Leu Lys Gly Lys Asn Thr Glu Asn Met 65 70 75

Gly Phe Tyr Gly Thr Leu Lys Met Ile Phe Tyr Lys Met Lys Arg 80 85 90 Gly Phe Tyr Gly Thr Leu Lys Met Ile Phe Tyr Lys Met Lys Arg 80 85 90

Lys Leu Asp His Gly Ser Glu Val Arg Ser Phe Ser Leu Gly Lys 95 100 105 Lys Leu Asp His Gly Ser Glu Val Arg Ser Phe Ser Leu Gly Lys 95 100 105

Lys Pro Cys Lys Val Ser Glu Tyr Thr Ser Thr Thr Gly Leu Val 110 115 120 Lys Pro Cys Lys Val Ser Glu Tyr Thr Ser Thr Thr Gly Leu Val 110 115 120

Pro Cys Ser Ala Thr Pro Thr Thr Phe Gly Asp Leu Arg Ala Ala 125 130 135 Pro Cys Ser Ala Thr Pro Thr Thr Phe Gly Asp Leu Arg Ala Ala 125 130 135

Asn Gly Gln Gly Gln Gln Arg Arg Arg Ile Thr Ser Val Gln Pro 140 145 150 Asn Gly Gln Gly Gln Gln Arg Arg Arg Ile Thr Ser Val Gln Pro 140 145 150

Pro Thr Gly Leu Gln Glu Trp Leu Lys Met Phe Gln Ser Trp Ser 155 160 165 Pro Thr Gly Leu Gln Glu Trp Leu Lys Met Phe Gln Ser Trp Ser 155 160 165

Gly Pro Glu Lys Leu Leu Ala Leu Asp Glu Leu Ile Asp Ser Cys 170 175 180 Gly Pro Glu Lys Leu Leu Ala Leu Asp Glu Leu Ile Asp Ser Cys 170 175 180

Glu Pro Thr Gln Val Lys His Met Met Gln Val Ile Glu Pro Gln 185 190 195 Glu Pro Thr Gln Val Lys His Met Met Gln Val Ile Glu Pro Gln 185 190 195

Phe Gln Arg Asp Phe Ile Ser Leu Leu Pro Lys Glu Leu Ala Leu 200 205 210 Phe Gln Arg Asp Phe Ile Ser Leu Leu Pro Lys Glu Leu Ala Leu 200 205 210

Tyr Val Leu Ser Phe Leu Glu Pro Lys Asp Leu Leu Gln Ala Ala 215 220 225 Tyr Val Leu Ser Phe Leu Glu Pro Lys Asp Leu Leu Gln Wing 215 215 225 225

Gln Thr Cys Arg Tyr Trp Arg Ile Leu Ala Glu Asp Asn Leu Leu 230 235 240 Gln Thr Cys Arg Tyr Trp Arg Ile Leu Wing Glu Asp Asn Leu Leu 230 235 240

Trp Arg Glu Lys Cys Lys Glu Glu Gly Ile Asp Glu Pro Leu His 245 250 255 Trp Arg Glu Lys Cys Lys Glu Glu Gly Ile Asp Glu Pro Leu His 245 250 255

Ile Lys Arg Arg Lys Val Ile Lys Pro Gly Phe Ile His Ser Pro 260 265 270 Ile Lys Arg Arg Lys Val Ile Lys Pro Gly Phe Ile His Ser Pro 260 265 270

Trp Lys Ser Ala Tyr Ile Arg Gln His Arg Ile Asp Thr Asn Trp 275 280 285 Trp Lys Ser Ala Tyr Ile Arg Gln His Arg Ile Asp Thr Asn Trp 275 280 285

Arg Arg Gly Glu Leu Lys Ser Pro Lys Val Leu Lys Gly His Asp 290 295 300 Arg Arg Gly Glu Leu Lys Ser Pro Lys Val Leu Lys Gly His Asp 290 295 300

Asp His Val Ile Thr Cys Leu Gln Phe Cys Gly Asn Arg Ile Val 305 310 315 Asp His Val Ile Thr Cys Leu Gln Phe Cys Gly Asn Arg Ile Val 305 310 315

Ser Gly Ser Asp Asp Asn Thr Leu Lys Val Trp Ser Ala Val Thr 320 325 330 Ser Gly Ser Asp Asp Asn Thr Leu Lys Val Trp Ser Ala Val Thr 320 325 330

Gly Lys Cys Leu Arg Thr Leu Val Gly His Thr Gly Gly Val Trp 335 340 345 Gly Lys Cys Leu Arg Thr Leu Val Gly His Thr Gly Gly Val Trp 335 340 345

Ser Ser Gln Met Arg Asp Asn Ile Ile Ile Ser Gly Ser Thr Asp Be Be Gln Met Arg Asp Asn Ile Ile Ile Be Gly Ser Thr Asp

350 355 360 350 355 360

Arg Thr Leu Lys Val Trp Asn Ala Glu Thr Gly Glu Cys Ile His 365 370 375 Arg Thr Leu Lys Val Trp Asn Ala Glu Thr Gly Glu Cys Ile His 365 370 375

Thr Leu Tyr Gly His Thr Ser Thr Val Arg Cys Met His Leu His 380 385 390 Thr Leu Tyr Gly His Thr Ser Thr Val Arg Cys Met His Leu His 380 385 390

Glu Lys Arg Val Val Ser Gly Ser Arg Asp Ala Thr Leu Arg Val 395 400 405 Glu Lys Arg Val Val Ser Gly Ser Arg Asp Wing Thr Leu Arg Val 395 400 405

Trp Asp Ile Glu Thr Gly Gln Cys Leu His Val Leu Met Gly His 410 415 420 Trp Asp Ile Glu Thr Gly Gln Cys Leu His Val Leu Met Gly His 410 415 420

Val Ala Ala Val Arg Cys Val Gln Tyr Asp Gly Arg Arg Val Val 425 430 435 Val Wing Wing Val Arg Cys Val Gln Tyr Asp Gly Arg Arg Val Val 425 430 435

Ser Gly Ala Tyr Asp Phe Met Val Lys Val Trp Asp Pro Glu Thr 440 445 450 Ser Gly Ala Tyr Asp Phe Met Val Lys Val Trp Asp Pro Glu Thr 440 445 450

Glu Thr Cys Leu His Thr Leu Gln Gly His Thr Asn Arg Val Tyr 455 460 465 Glu Thr Cys Leu His Thr Leu Gln Gly His Thr Asn Arg Val Tyr 455 460 465

Ser Leu Gln Phe Asp Gly Ile His Val Val Ser Gly Ser Leu Asp 470 475 480 Ser Leu Gln Phe Asp Gly Ile His Val Val Ser Gly Ser Leu Asp 470 475 480

Thr Ser Ile Arg Val Trp Asp Val Glu Thr Gly Asn Cys Ile His 485 490 495 Thr Ser Ile Arg Val Trp Asp Val Glu Thr Gly Asn Cys Ile His 485 490 495

Thr Leu Thr Gly His Gln Ser Leu Thr Ser Gly Met Glu Leu Lys 500 505 510 Thr Leu Thr Gly His Gln Ser Leu Thr Ser Gly Met Glu Leu Lys 500 505 510

Asp Asn Ile Leu Val Ser Gly Asn Ala Asp Ser Thr Val Lys Ile 515 520 525 Asp Asn Ile Leu Val Ser Gly Asn Ala Asp Ser Thr Val Lys Ile 515 520 525

Trp Asp Ile Lys Thr Gly Gln Cys Leu Gln Thr Leu Gln Gly Pro 530 535 540 Trp Asp Ile Lys Thr Gly Gln Cys Leu Gln Thr Leu Gln Gly Pro 530 535 540

Asn Lys His Gln Ser Ala Val Thr Cys Leu Gln Phe Asn Lys Asn 545 550 555 Asn Lys His Gln Ser Ala Val Thr Cys Leu Gln Phe Asn Lys Asn 545 550 555

Phe Val Ile Thr Ser Ser Asp Asp Gly Thr Val Lys Leu Trp Asp 560 565 570 Phe Val Ile Thr Ser Ser Asp Asp Gly Thr Val Lys Leu Trp Asp 560 565 570

Leu Lys Thr Gly Glu Phe Ile Arg Asn Leu Val Thr Leu Glu Ser 575 580 585 Leu Lys Thr Gly Glu Phe Ile Arg Asn Leu Val Thr Leu Glu Ser 575 580 585

Gly Gly Ser Gly Gly Val Val Trp Arg Ile Arg Ala Ser Asn Thr 590 595 600 Gly Gly Ser Gly Gly Val Val Trp Arg Ile Arg Ala Ser Asn Thr 590 595 600

Lys Leu Val Cys Ala Val Gly Ser Arg Asn Gly Thr Glu Glu Thr 605 610 615 Lys Leu Val Cys Wing Val Gly Ser Arg Asn Gly Thr Glu Glu Thr 605 610 615

Lys Leu Leu Val Leu Asp Phe Asp Val Asp Met Lys 620 625 Lys Leu Leu Val Leu Asp Phe Asp Val Asp Met Lys 620 625

<210> 43 <210> 43

<211> 1338 <211> 1338

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 43 Met Val Ser Tyr Trp Asp Thr Gly Val Leu Leu Cys Ala Leu Leu 1 5 10 15 <400> 43 Met Val Ser Tyr Trp Asp Thr Gly Val Leu Leu Cys Ala Leu Leu 1 5 10 15

Ser Cys Leu Leu Leu Thr Gly Ser Ser Ser Gly Ser Lys Leu Lys 20 25 30 Asp Pro Glu Leu Ser Leu Lys Gly Thr Gln His Ile Met Gln Ala 35 40 Be Cys Leu Leu Leu Thr Gly Be Be Be Gly Be Lys Leu Lys 20 25 30 Asp Pro Glu Leu Be Leu Lys Gly Thr Gln His Ile Met Gln Wing 35 40

Gly Gln Thr Leu His Leu Gln Cys Arg Gly Glu Ala Ala His Lys 50 55 60 Gly Gln Thr Leu His Leu Gln Cys Arg Gly Glu Ala Ala His Lys 50 55 60

Trp Ser Leu Pro Glu Met Val Ser Lys Glu Ser Glu Arg Leu Ser 65 70 75 Trp Ser Leu Pro Glu Met Val Ser Lys Glu Ser Glu Arg Leu Ser 65 70 75

Ile Thr Lys Ser Ala Cys Gly Arg Asn Gly Lys Gln Phe Cys Ser 80 85 90 Ile Thr Lys Ser Ala Cys Gly Arg Asn Gly Lys Gln Phe Cys Ser 80 85 90

Thr Leu Thr Leu Asn Thr Ala Gln Ala Asn His Thr Gly Phe Tyr 95 100 105 Thr Leu Thr Leu Asn Thr Gln Wing Asn His Thr Gly Phe Tyr 95 100 105

Ser Cys Lys Tyr Leu Ala Val Pro Thr Ser Lys Lys Lys Glu Thr 110 115 120 Ser Cys Lys Tyr Leu Ala Val Pro Thr Ser Lys Lys Lys Glu Thr 110 115 120

Glu Ser Ala Ile Tyr Ile Phe Ile Ser Asp Thr Gly Arg Pro Phe 125 130 135 Glu Ser Ala Ile Tyr Ile Phe Ile Ser Asp Thr Gly Arg Pro Phe 125 130 135

Val Glu Met Tyr Ser Glu Ile Pro Glu Ile Ile His Met Thr Glu 140 145 150 Val Glu Met Tyr Ser Glu Ile Pro Glu Ile Ile His Met Thr Glu 140 145 150

Gly Arg Glu Leu Val Ile Pro Cys Arg Val Thr Ser Pro Asn Ile 155 160 165 Gly Arg Glu Leu Val Ile Pro Cys Arg Val Thr Ser Pro Asn Ile 155 160 165

Thr Val Thr Leu Lys Lys Phe Pro Leu Asp Thr Leu Ile Pro Asp 170 175 180 Thr Val Thr Leu Lys Lys Phe Pro Leu Asp Thr Leu Ile Pro Asp 170 175 180

Gly Lys Arg Ile Ile Trp Asp Ser Arg Lys Gly Phe Ile Ile Ser 185 190 195 Gly Lys Arg Ile Ile Trp Asp Ser Arg Lys Gly Phe Ile Ile Ser 185 190 195

Asn Ala Thr Tyr Lys Glu Ile Gly Leu Leu Thr Cys Glu Ala Thr 200 205 210 Asn Ala Thr Tyr Lys Glu Ile Gly Leu Leu Thr Cys Glu Ala Thr 200 205 210

Val Asn Gly His Leu Tyr Lys Thr Asn Tyr Leu Thr His Arg Gln 215 220 225 Val Asn Gly His Leu Tyr Lys Thr Asn Tyr Leu Thr His Arg Gln 215 220 225

Thr Asn Thr Ile Ile Asp Val Gln Ile Ser Thr Pro Arg Pro Val 230 235 240 Thr Asn Thr Ile Ile Asp Val Gln Ile Ser Thr Pro Arg Pro Val 230 235 240

Lys Leu Leu Arg Gly His Thr Leu Val Leu Asn Cys Thr Ala Thr 245 250 255 Lys Leu Leu Arg Gly His Thr Leu Val Leu Asn Cys Thr Ala Thr 245 250 255

Thr Pro Leu Asn Thr Arg Val Gln Met Thr Trp Ser Tyr Pro Asp 260 265 270 Thr Pro Leu Asn Thr Arg Val Gln Met Thr Trp Ser Tyr Pro Asp 260 265 270

Glu Lys Asn Lys Arg Ala Ser Val Arg Arg Arg Ile Asp Gln Ser 275 280 285 Glu Lys Asn Lys Arg Ala Ser Val Arg Arg Arg Ile Asp Gln Ser 275 280 285

Asn Ser His Ala Asn Ile Phe Tyr Ser Val Leu Thr Ile Asp Lys 290 295 300 Asn Ser His Ala Asn Ile Phe Tyr Ser Val Leu Thr Ile Asp Lys 290 295 300

Met Gln Asn Lys Asp Lys Gly Leu Tyr Thr Cys Arg Val Arg Ser 305 310 315 Met Gln Asn Lys Asp Lys Gly Leu Tyr Thr Cys Arg Val Arg Ser 305 310 315

Gly Pro Ser Phe Lys Ser Val Asn Thr Ser Val His Ile Tyr Asp 320 325 330 Gly Pro Ser Phe Lys Ser Val Asn Thr Ser Val His Ile Tyr Asp 320 325 330

Lys Ala Phe Ile Thr Val Lys His Arg Lys Gln Gln Val Leu Glu 335 340 345 Lys Wing Phe Ile Thr Val Lys His Arg Lys Gln Gln Val Leu Glu 335 340 345

Thr Val Ala Gly Lys Arg Ser Tyr Arg Leu Ser Met Lys Val Lys 350 355 360 Thr Val Wing Gly Lys Arg Ser Tyr Arg Leu Ser Met Lys Val Lys 350 355 360

Ala Phe Pro Ser Pro Glu Val Val Trp Leu Lys Asp Gly Leu Pro 365 370 Wing Phe Pro Ser Pro Glu Val Val Trp Leu Lys Asp Gly Leu Pro 365 370

Ala Thr Glu Lys Ser Ala Arg Tyr Leu Thr Arg Gly Tyr Ser Leu 380 385 Wing Thr Glu Lys Ser Wing Arg Tyr Leu Thr Arg Gly Tyr Ser Leu 380 385

Ile Ile Lys Asp Val Thr Glu Glu Asp Ala Gly Asn Tyr Thr Ile 395 400 405 Ile Ile Lys Asp Val Thr Glu Glu Asp Wing Gly Asn Tyr Thr Ile 395 400 405

Leu Leu Ser Ile Lys Gln Ser Asn Val Phe Lys Asn Leu Thr Ala 410 415 420 Leu Leu Ser Ile Lys Gln Ser Asn Val Phe Lys Asn Leu Thr Wing 410 415 420

Thr Leu Ile Val Asn Val Lys Pro Gln Ile Tyr Glu Lys Ala Val 425 430 435 Thr Leu Ile Val Asn Val Lys Pro Gln Ile Tyr Glu Lys Ala Val 425 430 435

Ser Ser Phe Pro Asp Pro Ala Leu Tyr Pro Leu Gly Ser Arg Gln 440 445 450 Ser Ser Phe Pro Asp Pro Ala Leu Tyr Pro Leu Gly Ser Arg Gln 440 445 450

Ile Leu Thr Cys Thr Ala Tyr Gly Ile Pro Gln Pro Thr Ile Lys 455 460 465 Ile Leu Thr Cys Thr Wing Tyr Gly Ile Pro Gln Pro Thr Ile Lys 455 460 465

Trp Phe Trp His Pro Cys Asn His Asn His Ser Glu Ala Arg Cys 470 475 480 Trp Phe Trp His Pro Cys Asn His Asn His Ser Glu Ala Arg Cys 470 475 480

Asp Phe Cys Ser Asn Asn Glu Glu Ser Phe Ile Leu Asp Ala Asp 485 490 495 Asp Phe Cys Ser Asn Asn Glu Glu Ser Phe Ile Leu Asp Ala Asp 485 490 495

Ser Asn Met Gly Asn Arg Ile Glu Ser Ile Thr Gln Arg Met Ala 500 505 510 Ser Asn Met Gly Asn Arg Ile Glu Ser Ile Thr Gln Arg Met Ala 500 505 510

Ile Ile Glu Gly Lys Asn Lys Met Ala Ser Thr Leu Val Val Ala 515 520 525 Ile Ile Glu Gly Lys Asn Lys Met Ala Ser Thr Leu Val Val Ala 515 520 525

Asp Ser Arg Ile Ser Gly Ile Tyr Ile Cys Ile Ala Ser Asn Lys 530 535 540 Asp Ser Arg Ile Ser Gly Ile Tyr Ile Cys Ile Ala Ser Asn Lys 530 535 540

Val Gly Thr Val Gly Arg Asn Ile Ser Phe Tyr Ile Thr Asp Val 545 550 555 Val Gly Thr Val Gly Arg Asn Ile Ser Phe Tyr Ile Thr Asp Val 545 550 555

Pro Asn Gly Phe His Val Asn Leu Glu Lys Met Pro Thr Glu Gly 560 565 570 Pro Asn Gly Phe His Val Asn Leu Glu Lys Met Pro Thr Glu Gly 560 565 570

Glu Asp Leu Lys Leu Ser Cys Thr Val Asn Lys Phe Leu Tyr Arg 575 580 585 Glu Asp Leu Lys Leu Ser Cys Thr Val Asn Lys Phe Leu Tyr Arg 575 580 585

Asp Val Thr Trp Ile Leu Leu Arg Thr Val Asn Asn Arg Thr Met 590 595 600 Asp Val Thr Trp Ile Leu Leu Arg Thr Val Asn Asn Arg Thr Met 590 595 600

His Tyr Ser Ile Ser Lys Gln Lys Met Ala Ile Thr Lys Glu His 605 610 615 His Tyr Ser Ile Ser Lys Gln Lys Met Ile Thr Lys Glu His 605 610 615

Ser Ile Thr Leu Asn Leu Thr Ile Met Asn Val Ser Leu Gln Asp 620 625 630 Ser Ile Thr Leu Asn Leu Thr Ile Met Asn Val Ser Leu Gln Asp 620 625 630

Ser Gly Thr Tyr Ala Cys Arg Ala Arg Asn Val Tyr Thr Gly Glu 635 640 645 Ser Gly Thr Tyr Ala Cys Arg Ala Arg Asn Val Tyr Thr Gly Glu 635 640 645

Glu Ile Leu Gln Lys Lys Glu Ile Thr Ile Arg Asp Gln Glu Ala 650 655 660 Glu Ile Leu Gln Lys Lys Glu Ile Thr Ile Arg Asp Gln Glu Ala 650 655 660

Pro Tyr Leu Leu Arg Asn Leu Ser Asp His Thr Val Ala Ile Ser 665 670 675 Pro Tyr Leu Leu Arg Asn Leu Ser Asp His Thr Val Ala Ile Ser 665 670 675

Ser Ser Thr Thr Leu Asp Cys His Ala Asn Gly Val Pro Glu Pro 680 685 690 Ser Ser Thr Thr Leu Asp Cys His Ala Asn Gly Val Pro Glu Pro 680 685 690

Gln Ile Thr Trp Phe Lys Asn Asn His Lys Ile Gln Gln Glu Pro 695 700 705 Gln Ile Thr Trp Phe Lys Asn Asn His Lys Ile Gln Gln Glu Pro 695 700 705

Gly Ile Ile Leu Gly Pro Gly Ser Ser Thr Leu Phe Ile Glu Arg Gly Ile Ile Leu Gly Pro Gly Ser Ser Thr Leu Phe Ile Glu Arg

710 715 710 715

Val Thr Glu Glu Asp Glu Gly Val Tyr His Cys Lys Ala Thr Asn 725 730 735 Val Thr Glu Glu Asp Glu Gly Val Tyr His Cys Lys Ala Thr Asn 725 730 735

Gln Lys Gly Ser Val Glu Ser Ser Ala Tyr Leu Thr Val Gln Gly 740 745 750 Gln Lys Gly Ser Val Glu Ser Ser Ala Tyr Leu Thr Val Gln Gly 740 745 750

Thr Ser Asp Lys Ser Asn Leu Glu Leu Ile Thr Leu Thr Cys Thr 755 760 765 Thr Ser Asp Lys Ser Asn Leu Glu Leu Ile Thr Leu Thr Cys Thr 755 760 765

Cys Val Ala Ala Thr Leu Phe Trp Leu Leu Leu Thr Leu Phe Ile 770 775 780 Cys Val Wing Wing Thr Leu Phe Trp Leu Leu Leu Thr Leu Phe Ile 770 775 780

Arg Lys Met Lys Arg Ser Ser Ser Glu Ile Lys Thr Asp Tyr Leu 785 790 795 Arg Lys Met Lys Arg Be Be Be Glu Ile Lys Thr Asp Tyr Leu 785 790 795

Ser Ile Ile Met Asp Pro Asp Glu Val Pro Leu Asp Glu Gln Cys 800 805 810 Ser Ile Ile Met Asp Pro Asp Glu Val Pro Leu Asp Glu Gln Cys 800 805 810

Glu Arg Leu Pro Tyr Asp Ala Ser Lys Trp Glu Phe Ala Arg Glu 815 820 825 Glu Arg Leu Pro Tyr Asp Ala Ser Lys Trp Glu Phe Ala Arg Glu 815 820 825

Arg Leu Lys Leu Gly Lys Ser Leu Gly Arg Gly Ala Phe Gly Lys 830 835 840 Arg Leu Lys Leu Gly Lys Ser Leu Gly Arg Gly Ala Phe Gly Lys 830 835 840

Val Val Gln Ala Ser Ala Phe Gly Ile Lys Lys Ser Pro Thr Cys 845 850 855 Val Val Gln Wing Ser Wing Phe Gly Ile Lys Lys Ser Pro Thr Cys 845 850 855

Arg Thr Val Ala Val Lys Met Leu Lys Glu Gly Ala Thr Ala Ser 860 865 870 Arg Thr Val Wing Val Lys Met Leu Lys Glu Gly Wing Thr Wing Ser 860 865 870

Glu Tyr Lys Ala Leu Met Thr Glu Leu Lys Ile Leu Thr His Ile 875 880 885 Glu Tyr Lys Ala Leu Met Thr Glu Leu Lys Ile Leu Thr His Ile 875 880 885

Gly His His Leu Asn Val Val Asn Leu Leu Gly Ala Cys Thr Lys 890 895 900 Gly His His Leu Asn Val Val Asn Leu Leu Gly Ala Cys Thr Lys 890 895 900

Gln Gly Gly Pro Leu Met Val Ile Val Glu Tyr Cys Lys Tyr Gly 905 910 915 Gln Gly Gly Pro Leu Met Val Ile Val Glu Tyr Cys Lys Tyr Gly 905 910 915

Asn Leu Ser Asn Tyr Leu Lys Ser Lys Arg Asp Leu Phe Phe Leu 920 925 930 Asn Leu Ser Asn Tyr Leu Lys Ser Lys Arg Asp Leu Phe Phe Leu 920 925 930

Asn Lys Asp Ala Ala Leu His Met Glu Pro Lys Lys Glu Lys Met 935 940 945 Asn Lys Asp Ala Wing Leu His Met Glu Pro Lys Lys Glu Lys Met 935 940 945

Glu Pro Gly Leu Glu Gln Gly Lys Lys Pro Arg Leu Asp Ser Val 950 955 960 Glu Pro Gly Leu Glu Gln Gly Lys Lys Pro Arg Leu Asp Ser Val 950 955 960

Thr Ser Ser Glu Ser Phe Ala Ser Ser Gly Phe Gln Glu Asp Lys 965 970 975 Thr Be Be Glu Be Phe Ala Be Be Gly Phe Gln Glu Asp Lys 965 970 975

Ser Leu Ser Asp Val Glu Glu Glu Glu Asp Ser Asp Gly Phe Tyr 980 985 990 Be Leu Be Asp Val Glu Glu Glu Glu Asp Be Asp Gly Phe Tyr 980 985 990

Lys Glu Pro Ile Thr Met Glu Asp Leu Ile Ser Tyr Ser Phe Gln 995 1000 1005 Lys Glu Pro Ile Thr Met Glu Asp Leu Ile Ser Tyr Ser Phe Gln 995 1000 1005

Val Ala Arg Gly Met Glu Phe Leu Ser Ser Arg Lys Cys Ile His 1010 1015 1020 Val Ala Arg Gly Met Glu Phe Leu Ser Ser Arg Lys Cys Ile His 1010 1015 1020

Arg Asp Leu Ala Ala Arg Asn Ile Leu Leu Ser Glu Asn Asn Val 1025 1030 1035 Arg Asp Leu Wing Wing Arg Asn Ile Leu Leu Ser Glu Asn Asn Val 1025 1030 1035

Val Lys Ile Cys Asp Phe Gly Leu Ala Arg Asp Ile Tyr Lys Asn 1040 1045 1050 Val Lys Ile Cys Asp Phe Gly Leu Ala Arg Asp Ile Tyr Lys Asn 1040 1045 1050

Pro Asp Tyr Val Arg Lys Gly Asp Thr Arg Leu Pro Leu Lys Trp 1055 1060 1065 Pro Asp Tyr Val Arg Lys Gly Asp Thr Arg Leu Pro Leu Lys Trp 1055 1060 1065

Met Ala Pro Glu Ser Ile Phe Asp Lys Ile Tyr Ser Thr Lys Ser 1070 1075 1080 Met Wing Pro Glu Ser Ile Phe Asp Lys Ile Tyr Ser Thr Lys Ser 1070 1075 1080

Asp Val Trp Ser Tyr Gly Val Leu Leu Trp Glu Ile Phe Ser Leu 1085 1090 1095 Asp Val Trp Ser Tyr Gly Val Leu Leu Trp Glu Ile Phe Ser Leu 1085 1090 1095

Gly Gly Ser Pro Tyr Pro Gly Val Gln Met Asp Glu Asp Phe Cys 1100 1105 1110 Gly Gly Ser Pro Tyr Pro Gly Val Gln Met Asp Glu Asp Phe Cys 1100 1105 1110

Ser Arg Leu Arg Glu Gly Met Arg Met Arg Ala Pro Glu Tyr Ser 1115 1120 1125 Ser Arg Leu Arg Glu Gly Met Arg Met Arg Ala Pro Glu Tyr Ser 1115 1120 1125

Thr Pro Glu Ile Tyr Gln Ile Met Leu Asp Cys Trp His Arg Asp 1130 1135 1140 Thr Pro Glu Ile Tyr Gln Ile Met Leu Asp Cys Trp His Arg Asp 1130 1135 1140

Pro Lys Glu Arg Pro Arg Phe Ala Glu Leu Val Glu Lys Leu Gly 1145 1150 1155 Pro Lys Glu Arg Pro Arg Phe Ala Glu Leu Val Glu Lys Leu Gly 1145 1150 1155

Asp Leu Leu Gln Ala Asn Val Gln Gln Asp Gly Lys Asp Tyr Ile 1160 1165 1170 Asp Leu Leu Gln Wing Asn Val Gln Gln Asp Gly Lys Asp Tyr Ile 1160 1165 1170

Pro Ile Asn Ala Ile Leu Thr Gly Asn Ser Gly Phe Thr Tyr Ser 1175 1180 1185 Pro Ile Asn Ala Ile Leu Thr Gly Asn Ser Gly Phe Thr Tyr Ser 1175 1180 1185

Thr Pro Ala Phe Ser Glu Asp Phe Phe Lys Glu Ser Ile Ser Ala 1190 1195 1200 Thr Pro Wing Phe Ser Glu Asp Phe Phe Lys Glu Ser Ile Ser Wing 1190 1195 1200

Pro Lys Phe Asn Ser Gly Ser Ser Asp Asp Val Arg Tyr Val Asn 1205 1210 1215 Pro Lys Phe Asn Ser Gly Ser Be Asp Asp Val Arg Tyr Val Asn 1205 1210 1215

Ala Phe Lys Phe Met Ser Leu Glu Arg Ile Lys Thr Phe Glu Glu 1220 1225 1230 Wing Phe Lys Phe Met Ser Leu Glu Arg Ile Lys Thr Phe Glu Glu 1220 1225 1230

Leu Leu Pro Asn Ala Thr Ser Met Phe Asp Asp Tyr Gln Gly Asp 1235 1240 1245 Leu Leu Pro Asn Ala Thr Ser Met Phe Asp Asp Tyr Gln Gly Asp 1235 1240 1245

Ser Ser Thr Leu Leu Ala Ser Pro Met Leu Lys Arg Phe Thr Trp 1250 1255 1260 Ser Ser Thr Leu Leu Ala Ser Pro Met Leu Lys Arg Phe Thr Trp 1250 1255 1260

Thr Asp Ser Lys Pro Lys Ala Ser Leu Lys Ile Asp Leu Arg Val 1265 1270 1275 Thr Asp Ser Lys Pro Lys Ala Ser Leu Lys Ile Asp Leu Arg Val 1265 1270 1275

Thr Ser Lys Ser Lys Glu Ser Gly Leu Ser Asp Val Ser Arg Pro 1280 1285 1290 Thr Ser Lys Ser Lys Glu Ser Gly Leu Ser Asp Val Ser Arg Pro 1280 1285 1290

Ser Phe Cys His Ser Ser Cys Gly His Val Ser Glu Gly Lys Arg 1295 1300 1305 Ser Phe Cys His Ser Ser Cys Gly His Val Ser Glu Gly Lys Arg 1295 1300 1305

Arg Phe Thr Tyr Asp His Ala Glu Leu Glu Arg Lys Ile Ala Cys 1310 1315 1320 Arg Phe Thr Tyr Asp His Ala Glu Leu Glu Arg Lys Ile Ala Cys 1310 1315 1320

Cys Ser Pro Pro Pro Asp Tyr Asn Ser Val Val Leu Tyr Ser Thr 1325 1330 1335 Cys Ser Pro Pro Pro Asp Tyr Asn Ser Val Val Leu Tyr Ser Thr 1325 1330 1335

Pro Pro Ile Pro Pro Ile

<210> 44 <210> 44

<211> 993 <211> 993

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 44 Met Pro Ala Leu Ala Arg Asp Gly Gly Gln Leu Pro Leu Leu Val 1 5 10 15 <400> 44 Met Pro Wing Leu Wing Arg Asp Gly Gly Gln Leu Pro Leu Leu Val 1 5 10 15

Val Phe Ser Ala Met Ile Phe Gly Thr Ile Thr Asn Gln Asp Leu 20 25 Val Phe Ser Wing Met Ile Phe Gly Thr Ile Thr Asn Gln Asp Leu 20 25

Pro Val Ile Lys Cys Val Leu Ile Asn His Lys Asn Asn Asp Ser 35 40 45 Pro Val Ile Lys Cys Val Leu Ile Asn His Lys Asn Asn Asp Ser 35 40 45

Ser Val Gly Lys Ser Ser Ser Tyr Pro Met Val Ser Glu Ser Pro 50 55 60 Be Val Gly Lys Be Be Be Tyr Pro Met Val Be Glu Be Pro 50 55 60

Glu Asp Leu Gly Cys Ala Leu Arg Pro Gln Ser Ser Gly Thr Val 65 70 75 Glu Asp Leu Gly Cys Ala Leu Arg Pro Gln Ser Ser Gly Thr Val 65 70 75

Tyr Glu Ala Ala Ala Val Glu Val Asp Val Ser Ala Ser Ile Thr 80 85 90 Tyr Glu Wing Wing Val Val Glu Val Asp Val Ser Wing Ser Ile Thr 80 85 90

Leu Gln Val Leu Val Asp Ala Pro Gly Asn Ile Ser Cys Leu Trp 95 100 105 Leu Gln Val Leu Val Asp Wing Pro Gly Asn Ile Ser Cys Leu Trp 95 100 105

Val Phe Lys His Ser Ser Leu Asn Cys Gln Pro His Phe Asp Leu 110 115 120 Val Phe Lys His Ser Ser Leu Asn Cys Gln Pro His Phe Asp Leu 110 115 120

Gln Asn Arg Gly Val Val Ser Met Val Ile Leu Lys Met Thr Glu 125 130 135 Gln Asn Arg Gly Val Val Ser Met Val Ile Leu Lys Met Thr Glu 125 130 135

Thr Gln Ala Gly Glu Tyr Leu Leu Phe Ile Gln Ser Glu Ala Thr 140 145 150 Thr Gln Wing Gly Glu Tyr Leu Leu Phe Ile Gln Ser Glu Wing Thr 140 145 150

Asn Tyr Thr Ile Leu Phe Thr Val Ser Ile Arg Asn Thr Leu Leu 155 160 165 Asn Tyr Thr Ile Leu Phe Thr Val Ser Ile Arg Asn Thr Leu Leu 155 160 165

Tyr Thr Leu Arg Arg Pro Tyr Phe Arg Lys Met Glu Asn Gln Asp 170 175 180 Tyr Thr Leu Arg Arg Pro Tyr Phe Arg Lys Met Glu Asn Gln Asp 170 175 180

Ala Leu Val Cys Ile Ser Glu Ser Val Pro Glu Pro Ile Val Glu 185 190 195 Ala Leu Val Cys Ile Ser Glu Ser Val Pro Glu Pro Ile Val Glu 185 190 195

Trp Val Leu Cys Asp Ser Gln Gly Glu Ser Cys Lys Glu Glu Ser 200 205 210 Trp Val Leu Cys Asp Ser Gln Gly Glu Ser Cys Lys Glu Glu Ser 200 205 210

Pro Ala Val Val Lys Lys Glu Glu Lys Val Leu His Glu Leu Phe 215 220 225 Pro Ala Val Val Lys Lys Glu Glu Lys Val Leu His Glu Leu Phe 215 220 225

Gly Thr Asp Ile Arg Cys Cys Ala Arg Asn Glu Leu Gly Arg Glu 230 235 240 Gly Thr Asp Ile Arg Cys Cys Ala Arg Asn Glu Leu Gly Arg Glu 230 235 240

Cys Thr Arg Leu Phe Thr Ile Asp Leu Asn Gln Thr Pro Gln Thr 245 250 255 Cys Thr Arg Leu Phe Thr Ile Asp Leu Asn Gln Thr Pro Gln Thr 245 250 255

Thr Leu Pro Gln Leu Phe Leu Lys Val Gly Glu Pro Leu Trp Ile 260 265 270 Thr Leu Pro Gln Leu Phe Leu Lys Val Gly Glu Pro Leu Trp Ile 260 265 270

Arg Cys Lys Ala Val His Val Asn His Gly Phe Gly Leu Thr Trp 275 280 285 Arg Cys Lys Ala Val His Val Asn His Gly Phe Gly Leu Thr Trp 275 280 285

Glu Leu Glu Asn Lys Ala Leu Glu Glu Gly Asn Tyr Phe Glu Met 290 295 300 Glu Leu Glu Asn Lys Ala Leu Glu Glu Gly Asn Tyr Phe Glu Met 290 295 300

Ser Thr Tyr Ser Thr Asn Arg Thr Met Ile Arg Ile Leu Phe Ala 305 310 315 Ser Thr Tyr Ser Thr Asn Arg Thr Met Ile Arg Ile Leu Phe Ala 305 310 315

Phe Val Ser Ser Val Ala Arg Asn Asp Thr Gly Tyr Tyr Thr Cys 320 325 330 Phe Val Ser Ser Val Ala Arg Asn Asp Thr Gly Tyr Tyr Thr Cys 320 325 330

Ser Ser Ser Lys His Pro Ser Gln Ser Ala Leu Val Thr Ile Val 335 340 345 Be Be Be Lys His Pro Be Gln Be Ala Leu Val Thr Ile Val 335 340 345

Glu Lys Gly Phe Ile Asn Ala Thr Asn Ser Ser Glu Asp Tyr Glu Glu Lys Gly Phe Ile Asn Ala Thr Asn Ser Ser Glu Asp Tyr Glu

350 355 350 355

Ile Asp Gln Tyr Glu Glu Phe Cys Phe Ser Val Arg Phe Lys Ala 365 370 375 Ile Asp Gln Tyr Glu Glu Phe Cys Phe Ser Val Arg Phe Lys Ala 365 370 375

Tyr Pro Gln Ile Arg Cys Thr Trp Thr Phe Ser Arg Lys Ser Phe 380 385 390 Tyr Pro Gln Ile Arg Cys Thr Trp Thr Phe Ser Arg Lys Ser Phe 380 385 390

Pro Cys Glu Gln Lys Gly Leu Asp Asn Gly Tyr Ser Ile Ser Lys 395 400 405 Pro Cys Glu Gln Lys Gly Leu Asp Asn Gly Tyr Ser Ile Ser Lys 395 400 405

Phe Cys Asn His Lys His Gln Pro Gly Glu Tyr Ile Phe His Ala 410 415 420 Phe Cys Asn His Lys His Gln Pro Gly Glu Tyr Ile Phe His Ala 410 415 420

Glu Asn Asp Asp Ala Gln Phe Thr Lys Met Phe Thr Leu Asn Ile 425 430 435 Glu Asn Asp Asp Wing Gln Phe Thr Lys Met Phe Thr Leu Asn Ile 425 430 435

Arg Arg Lys Pro Gln Val Leu Ala Glu Ala Ser Ala Ser Gln Ala 440 445 450 Arg Arg Lys Pro Gln Val Leu Wing Glu Ala Ser Ala Ser Gln Ala 440 445 450

Ser Cys Phe Ser Asp Gly Tyr Pro Leu Pro Ser Trp Thr Trp Lys 455 460 465 Ser Cys Phe Ser Asp Gly Tyr Pro Leu Pro Ser Trp Thr Trp Lys 455 460 465

Lys Cys Ser Asp Lys Ser Pro Asn Cys Thr Glu Glu Ile Thr Glu 470 475 480 Lys Cys Ser Asp Lys Ser Pro Asn Cys Thr Glu Glu Ile Thr Glu 470 475 480

Gly Val Trp Asn Arg Lys Ala Asn Arg Lys Val Phe Gly Gln Trp 485 490 495 Gly Val Trp Asn Arg Lys Wing Asn Arg Lys Val Phe Gly Gln Trp 485 490 495

Val Ser Ser Ser Thr Leu Asn Met Ser Glu Ala Ile Lys Gly Phe 500 505 510 Val Ser Ser Ser Thr Leu Asn Met Ser Glu Ala Ile Lys Gly Phe 500 505 510

Leu Val Lys Cys Cys Ala Tyr Asn Ser Leu Gly Thr Ser Cys Glu 515 520 525 Leu Val Lys Cys Cys Ala Tyr Asn Ser Leu Gly Thr Ser Cys Glu 515 520 525

Thr Ile Leu Leu Asn Ser Pro Gly Pro Phe Pro Phe Ile Gln Asp 530 535 540 Thr Ile Leu Leu Asn Ser Pro Gly Pro Phe Pro Phe Ile Gln Asp 530 535 540

Asn Ile Ser Phe Tyr Ala Thr Ile Gly Val Cys Leu Leu Phe Ile 545 550 555 Asn Ile Ser Phe Tyr Ala Thr Ile Gly Val Cys Leu Leu Phe Ile 545 550 555

Val Val Leu Thr Leu Leu Ile Cys His Lys Tyr Lys Lys Gln Phe 560 565 570 Val Val Leu Thr Leu Leu Ile Cys His Lys Tyr Lys Lys Gln Phe 560 565 570

Arg Tyr Glu Ser Gln Leu Gln Met Val Gln Val Thr Gly Ser Ser 575 580 585 Arg Tyr Glu Ser Gln Leu Gln Met Val Gln Val Thr Gly Ser Ser 575 580 585

Asp Asn Glu Tyr Phe Tyr Val Asp Phe Arg Glu Tyr Glu Tyr Asp 590 595 600 Asp Asn Glu Tyr Phe Tyr Val Asp Phe Arg Glu Tyr Glu Tyr Asp 590 595 600

Leu Lys Trp Glu Phe Pro Arg Glu Asn Leu Glu Phe Gly Lys Val 605 610 615 Leu Lys Trp Glu Phe Pro Arg Glu Asn Leu Glu Phe Gly Lys Val 605 610 615

Leu Gly Ser Gly Ala Phe Gly Lys Val Met Asn Ala Thr Ala Tyr 620 625 630 Leu Gly Ser Gly Ala Phe Gly Lys Val Met Asn Ala Thr Ala Tyr 620 625 630

Gly Ile Ser Lys Thr Gly Val Ser Ile Gln Val Ala Val Lys Met 635 640 645 Gly Ile Ser Lys Thr Gly Val Ser Ile Gln Val Ala Val Lys Met 635 640 645

Leu Lys Glu Lys Ala Asp Ser Ser Glu Arg Glu Ala Leu Met Ser 650 655 660 Leu Lys Glu Lys Ala Asp Ser Ser Glu Arg Glu Ala Leu Met Ser 650 655 660

Glu Leu Lys Met Met Thr Gln Leu Gly Ser His Glu Asn Ile Val 665 670 675 Glu Leu Lys Met Met Thr Gln Leu Gly Ser His Glu Asn Ile Val 665 670 675

Asn Leu Leu Gly Ala Cys Thr Leu Ser Gly Pro Ile Tyr Leu Ile 680 685 Asn Leu Leu Gly Ala Cys Thr Leu Ser Gly Pro Ile Tyr Leu Ile 680 685

Phe Glu Tyr Cys Cys Tyr Gly Asp Leu Leu Asn Tyr Leu Arg Ser 695 700 705 Phe Glu Tyr Cys Cys Tyr Gly Asp Leu Leu Asn Tyr Leu Arg Ser 695 700 705

Lys Arg Glu Lys Phe His Arg Thr Trp Thr Glu Ile Phe Lys Glu 710 715 720 Lys Arg Glu Lys Phe His Arg Thr Trp Thr Glu Ile Phe Lys Glu 710 715 720

His Asn Phe Ser Phe Tyr Pro Thr Phe Gln Ser His Pro Asn Ser 725 730 735 His Asn Phe Ser Phe Tyr Pro Thr Phe Gln Ser His Pro Asn Ser 725 730 735

Ser Met Pro Gly Ser Arg Glu Val Gln Ile His Pro Asp Ser Asp 740 745 750 Ser Met Pro Gly Ser Arg Glu Val Gln Ile His Pro Asp Ser Asp 740 745 750

Gln Ile Ser Gly Leu His Gly Asn Ser Phe His Ser Glu Asp Glu 755 760 765 Gln Ile Ser Gly Leu His Gly Asn Ser Phe His Ser Glu Asp Glu 755 760 765

Ile Glu Tyr Glu Asn Gln Lys Arg Leu Glu Glu Glu Glu Asp Leu 770 775 780 Ile Glu Tyr Glu Asn Gln Lys Arg Leu Glu Glu Glu Glu Glu Asp Leu 770 775 780

Asn Val Leu Thr Phe Glu Asp Leu Leu Cys Phe Ala Tyr Gln Val 785 790 795 Asn Val Leu Thr Phe Glu Asp Leu Leu Cys Phe Ala Tyr Gln Val 785 790 795

Ala Lys Gly Met Glu Phe Leu Glu Phe Lys Ser Cys Val His Arg 800 805 810 Wing Lys Gly Met Glu Phe Leu Glu Phe Lys Ser Cys Val His Arg 800 805 810

Asp Leu Ala Ala Arg Asn Val Leu Val Thr His Gly Lys Val Val 815 820 825 Asp Leu Wing Wing Arg Asn Val Leu Val Thr His Gly Lys Val Val 815 820 825

Lys Ile Cys Asp Phe Gly Leu Ala Arg Asp Ile Met Ser Asp Ser 830 835 840 Lys Ile Cys Asp Phe Gly Leu Ala Arg Asp Ile Met Ser Asp Ser 830 835 840

Asn Tyr Val Val Arg Gly Asn Ala Arg Leu Pro Val Lys Trp Met 845 850 855 Asn Tyr Val Val Arg Gly Asn Ala Arg Leu Pro Val Lys Trp Met 845 850 855

Ala Pro Glu Ser Leu Phe Glu Gly Ile Tyr Thr Ile Lys Ser Asp 860 865 870 Wing Pro Glu Ser Leu Phe Glu Gly Ile Tyr Thr Ile Lys Ser Asp 860 865 870

Val Trp Ser Tyr Gly Ile Leu Leu Trp Glu Ile Phe Ser Leu Gly 875 880 885 Val Trp Ser Tyr Gly Ile Leu Leu Trp Glu Ile Phe Ser Leu Gly 875 880 885

Val Asn Pro Tyr Pro Gly Ile Pro Val Asp Ala Asn Phe Tyr Lys 890 895 900 Val Asn Pro Tyr Pro Gly Ile Pro Val Asp Wing Asn Phe Tyr Lys 890 895 900

Leu Ile Gln Asn Gly Phe Lys Met Asp Gln Pro Phe Tyr Ala Thr 905 910 915 Leu Ile Gln Asn Gly Phe Lys Met Asp Gln Pro Phe Tyr Ala Thr 905 910 915

Glu Glu Ile Tyr Ile Ile Met Gln Ser Cys Trp Ala Phe Asp Ser 920 925 930 Glu Glu Ile Tyr Ile Ile Met Gln Ser Cys Trp Ala Phe Asp Ser 920 925 930

Arg Lys Arg Pro Ser Phe Pro Asn Leu Thr Ser Phe Leu Gly Cys 935 940 945 Arg Lys Arg Pro Ser Phe Pro Asn Leu Thr Ser Phe Leu Gly Cys 935 940 945

Gln Leu Ala Asp Ala Glu Glu Ala Met Tyr Gln Asn Val Asp Gly 950 955 960 Gln Leu Wing Asp Wing Glu Glu Wing Met Tyr Gln Asn Val Asp Gly 950 955 960

Arg Val Ser Glu Cys Pro His Thr Tyr Gln Asn Arg Arg Pro Phe 965 970 975 Arg Val Ser Glu Cys Pro His Thr Tyr Gln Asn Arg Arg Pro Phe 965 970 975

Ser Arg Glu Met Asp Leu Gly Leu Leu Ser Pro Gln Ala Gln Val 980 985 990 Ser Arg Glu Met Asp Leu Gly Leu Leu Ser Pro Gln Wing Gln Val 980 985 990

Glu Asp Ser Glu Asp Ser

<210> 45 <210> 45

<211> 2551 <211> 2551

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 45<400> 45

Met Leu Gly Thr Gly Pro Ala Ala Ala Thr Thr Ala Ala Thr Thr 1 5 10 15 Met Leu Gly Thr Gly Pro Wing Wing Thr Thr Wing Wing Thr Thr 1 5 10 15

Ser Ser Asn Val Ser Val Leu Gln Gln Phe Ala Ser Gly Leu Lys 20 25 30 Be Be Asn Val Be Val Leu Gln Gln Phe Ala Be Gly Leu Lys 20 25 30

Ser Arg Asn Glu Glu Thr Arg Ala Lys Ala Ala Lys Glu Leu Gln 35 40 45 Ser Arg Asn Glu Glu Thr Arg Wing Lys Wing Wing Lys Glu Leu Gln 35 40 45

His Tyr Val Thr Met Glu Leu Arg Glu Met Ser Gln Glu Glu Ser 50 55 60 His Tyr Val Thr Met Glu Leu Arg Glu Met Ser Gln Glu Glu Ser 50 55 60

Thr Arg Phe Tyr Asp Gln Leu Asn His His Ile Phe Glu Leu Val 65 70 75 Thr Arg Phe Tyr Asp Gln Leu Asn His His Ile Phe Glu Leu Val 65 70 75

Ser Ser Ser Asp Ala Asn Glu Arg Lys Gly Gly Ile Leu Ala Ile 80 85 90 Be Be Be Asp Wing Asn Glu Arg Lys Gly Gly Ile Leu Wing Ile 80 85 90

Ala Ser Leu Ile Gly Val Glu Gly Gly Asn Ala Thr Arg Ile Gly 95 100 105 Wing Ser Leu Ile Gly Val Glu Gly Gly Asn Wing Thr Arg Ile Gly 95 100 105

Arg Phe Ala Asn Tyr Leu Arg Asn Leu Leu Pro Ser Asn Asp Pro 110 115 120 Arg Phe Ala Asn Tyr Leu Arg Asn Leu Leu Pro Ser Asn Asp Pro 110 115 120

Val Val Met Glu Met Ala Ser Lys Ala Ile Gly Arg Leu Ala Met 125 130 135 Val Val Met Glu Met Wing Ser Lys Wing Ile Gly Arg Leu Wing Met 125 130 135

Ala Gly Asp Thr Phe Thr Ala Glu Tyr Val Glu Phe Glu Val Lys 140 145 150 Wing Gly Asp Thr Phe Thr Wing Glu Tyr Val Glu Phe Glu Val Lys 140 145 150

Arg Ala Leu Glu Trp Leu Gly Ala Asp Arg Asn Glu Gly Arg Arg 155 160 165 Arg Ala Leu Glu Trp Leu Gly Ala Asp Arg Asn Glu Gly Arg Arg 155 160 165

His Ala Ala Val Leu Val Leu Arg Glu Leu Ala Ile Ser Val Pro 170 175 180 His Wing Wing Val Leu Val Leu Arg Glu Leu Wing Ile Ser Val Pro 170 175 180

Thr Phe Phe Phe Gln Gln Val Gln Pro Phe Phe Asp Asn Ile Phe 185 190 195 Thr Phe Phe Phe Gln Gln Val Gln Pro Phe Phe Asp Asn Ile Phe 185 190 195

Val Ala Val Trp Asp Pro Lys Gln Ala Ile Arg Glu Gly Ala Val 200 205 210 Val Wing Val Trp Asp Pro Lys Gln Wing Ile Arg Glu Gly Wing Val 200 205 210

Ala Ala Leu Arg Ala Cys Leu Ile Leu Thr Thr Gln Arg Glu Pro 215 220 225 Wing Wing Leu Arg Wing Cys Leu Ile Leu Thr Thr Gln Arg Glu Pro 215 220 225

Lys Glu Met Gln Lys Pro Gln Trp Tyr Arg His Thr Phe Glu Glu 230 235 240 Lys Glu Met Gln Lys Pro Gln Trp Tyr Arg His Thr Phe Glu Glu 230 235 240

Ala Glu Lys Gly Phe Asp Glu Thr Leu Ala Lys Glu Lys Gly Met 245 250 255 Wing Glu Lys Gly Phe Asp Glu Thr Leu Wing Lys Glu Lys Gly Met 245 250 255

Asn Arg Asp Asp Arg Ile His Gly Ala Leu Leu Ile Leu Asn Glu 260 265 270 Asn Arg Asp Asp Arg Ile His Gly Ala Leu Leu Ile Leu Asn Glu 260 265 270

Leu Val Arg Ile Ser Ser Met Glu Gly Glu Arg Leu Arg Glu Glu 275 280 285 Leu Val Arg Ile Ser Ser Met Glu Gly Glu Arg Leu Arg Glu Glu 275 280 285

Met Glu Glu Ile Thr Gln Gln Gln Leu Val His Asp Lys Tyr Cys 290 295 300 Met Glu Glu Ile Thr Gln Gln Gln Leu Val His Asp Lys Tyr Cys 290 295 300

Lys Asp Leu Met Gly Phe Gly Thr Lys Pro Arg His Ile Thr Pro 305 310 315 Lys Asp Leu Met Gly Phe Gly Thr Lys Pro Arg His Ile Thr Pro 305 310 315

Phe Thr Ser Phe Gln Ala Val Gln Pro Gln Gln Ser Asn Ala Leu 320 325 330 Phe Thr Ser Phe Gln Ala Val Gln Pro Gln Gln Ser Asn Ala Leu 320 325 330

Val Gly Leu Leu Gly Tyr Ser Ser His Gln Gly Leu Met Gly Phe Val Gly Leu Leu Gly Tyr Ser Ser His Gln Gly Leu Met Gly Phe

335 340 335 340

Gly Thr Ser Pro Ser Pro Ala Lys Ser Thr Leu Val Glu Ser Arg 350 355 360 Gly Thr Ser Pro Ser Pro Ala Lys Ser Thr Leu Val Glu Ser Arg 350 355 360

Cys Cys Arg Asp Leu Met Glu Glu Lys Phe Asp Gln Val Cys Gln 365 370 375 Cys Cys Arg Asp Leu Met Glu Glu Lys Phe Asp Gln Val Cys Gln 365 370 375

Trp Val Leu Lys Cys Arg Asn Ser Lys Asn Ser Leu Ile Gln Met 380 385 390 Trp Val Leu Lys Cys Arg Asn Ser Lys Asn Ser Leu Ile Gln Met 380 385 390

Thr Ile Leu Asn Leu Leu Pro Arg Leu Ala Ala Phe Arg Pro Ser 395 400 405 Thr Ile Leu Asn Leu Leu Pro Arg Leu Wing Wing Phe Arg Pro Ser 395 400 405

Ala Phe Thr Asp Thr Gln Tyr Leu Gln Asp Thr Met Asn His Val 410 415 420 Wing Phe Thr Asp Thr Gln Tyr Leu Gln Asp Thr Met Asn His Val 410 415 420

Leu Ser Cys Val Lys Lys Glu Lys Glu Arg Thr Ala Ala Phe Gln 425 430 435 Leu Ser Cys Val Lys Lys Glu Lys Glu Arg Thr Ala Wing Phe Gln 425 430 435

Ala Leu Gly Leu Leu Ser Val Ala Val Arg Ser Glu Phe Lys Val 440 445 450 Wing Leu Gly Leu Leu Ser Val Wing Val Arg Ser Glu Phe Lys Val 440 445 450

Tyr Leu Pro Arg Val Leu Asp Ile Ile Arg Ala Ala Leu Pro Pro 455 460 465 Tyr Leu Pro Arg Val Leu Asp Ile Ile Arg Wing Wing Leu Pro Pro 455 460 465

Lys Asp Phe Ala His Lys Arg Gln Lys Ala Met Gln Val Asp Ala 470 475 480 Lys Asp Phe Wing His Lys Arg Gln Lys Wing Met Gln Val Asp Wing 470 475 480

Thr Val Phe Thr Cys Ile Ser Met Leu Ala Arg Ala Met Gly Pro 485 490 495 Thr Val Phe Thr Cys Ile Ser Met Leu Wing Arg Wing Met Gly Pro 485 490 495

Gly Ile Gln Gln Asp Ile Lys Glu Leu Leu Glu Pro Met Leu Ala 500 505 510 Gly Ile Gln Gln Asp Ile Lys Glu Leu Leu Glu Pro Met Leu Ala 500 505 510

Val Gly Leu Ser Pro Ala Leu Thr Ala Val Leu Tyr Asp Leu Ser 515 520 525 Val Gly Leu Ser Pro Ala Leu Thr Ala Val Leu Tyr Asp Leu Ser 515 520 525

Arg Gln Ile Pro Gln Leu Lys Lys Asp Ile Gln Asp Gly Leu Leu 530 535 540 Arg Gln Ile Pro Gln Leu Lys Lys Asp Ile Gln Asp Gly Leu Leu 530 535 540

Lys Met Leu Ser Leu Val Leu Met His Lys Pro Leu Arg His Pro 545 550 555 Lys Met Leu Ser Leu Val Leu Met His Lys Pro Leu Arg His Pro 545 550 555

Gly Met Pro Lys Gly Leu Ala His Gln Leu Ala Ser Pro Gly Leu 560 565 570 Gly Met Pro Lys Gly Leu Wing His Gln Leu Wing Being Pro Gly Leu 560 565 570

Thr Thr Leu Pro Glu Ala Ser Asp Val Gly Ser Ile Thr Leu Ala 575 580 585 Thr Thr Leu Pro Glu Ala Ser Asp Val Gly Ser Ile Thr Leu Ala 575 580 585

Leu Arg Thr Leu Gly Ser Phe Glu Phe Glu Gly His Ser Leu Thr 590 595 600 Leu Arg Thr Leu Gly Ser Phe Glu Phe Glu Gly His Ser Leu Thr 590 595 600

Gln Phe Val Arg His Cys Ala Asp His Phe Leu Asn Ser Glu His 605 610 615 Gln Phe Val Arg His Cys Ala Asp His Phe Leu Asn Ser Glu His 605 610 615

Lys Glu Ile Arg Met Glu Ala Ala Arg Thr Cys Ser Arg Leu Leu 620 625 630 Lys Glu Ile Arg Met Glu Ala Wing Arg Thr Cys Ser Arg Leu Leu 620 625 630

Thr Pro Ser Ile His Leu Ile Ser Gly His Ala His Val Val Ser 635 640 645 Thr Pro Ser Ile His Leu Ile Ser Gly His Ala His Val Val Ser 635 640 645

Gln Thr Ala Val Gln Val Val Ala Asp Val Leu Ser Lys Leu Leu 650 655 660 Gln Thr Val Wing Gln Val Val Wing Asp Val Leu Ser Lys Leu Leu 650 655 660

Val Val Gly Ile Thr Asp Pro Asp Pro Asp Ile Arg Tyr Cys Val 665 670 Val Val Gly Ile Thr Asp Pro Asp Pro Asp Ile Arg Tyr Cys Val 665 670

Leu Ala Ser Leu Asp Glu Arg Phe Asp Ala His Leu Ala Gln Ala 680 685 Leu Ala Ser Leu Asp Glu Arg Phe Asp Ala His Leu Gln Wing 680 685

Glu Asn Leu Gln Ala Leu Phe Val Ala Leu Asn Asp Gln Val Phe 695 700 705 Glu Asn Leu Gln Ala Leu Phe Val Ala Leu Asn Asp Gln Val Phe 695 700 705

Glu Ile Arg Glu Leu Ala Ile Cys Thr Val Gly Arg Leu Ser Ser 710 715 720 Glu Ile Arg Glu Leu Ile Wing Cys Thr Val Gly Arg Leu Ser Ser 710 715 720

Met Asn Pro Ala Phe Val Met Pro Phe Leu Arg Lys Met Leu Ile 725 730 735 Met Asn Pro Wing Phe Val Met Pro Phe Leu Arg Lys Met Leu Ile 725 730 735

Gln Ile Leu Thr Glu Leu Glu His Ser Gly Ile Gly Arg Ile Lys 740 745 750 Gln Ile Leu Thr Glu Leu Glu His Ser Gly Ile Gly Arg Ile Lys 740 745 750

Glu Gln Ser Ala Arg Met Leu Gly His Leu Val Ser Asn Ala Pro 755 760 765 Glu Gln Ser Ala Arg Met Leu Gly His Leu Val Ser Asn Ala Pro 755 760 765

Arg Leu Ile Arg Pro Tyr Met Glu Pro Ile Leu Lys Ala Leu Ile 770 775 780 Arg Leu Ile Arg Pro Tyr Met Glu Pro Ile Leu Lys Ala Leu Ile 770 775 780

Leu Lys Leu Lys Asp Pro Asp Pro Asp Pro Asn Pro Gly Val Ile 785 790 795 Leu Lys Leu Lys Asp Pro Asp Pro Asp Pro Asn Pro Gly Val Ile 785 790 795

Asn Asn Val Leu Ala Thr Ile Gly Glu Leu Ala Gln Val Ser Gly 800 805 810 Asn Asn Val Leu Wing Thr Ile Gly Glu Leu Wing Gln Val Ser Gly 800 805 810

Leu Glu Met Arg Lys Trp Val Asp Glu Leu Phe Ile Ile Ile Met 815 820 825 Leu Glu Met Arg Lys Trp Val Asp Glu Leu Phe Ile Ile Ile Met 815 820 825

Asp Met Leu Gln Asp Ser Ser Leu Leu Ala Lys Arg Gln Val Ala 830 835 840 Asp Met Leu Gln Asp Ser Ser Leu Leu Ala Lys Arg Gln Val Ala 830 835 840

Leu Trp Thr Leu Gly Gln Leu Val Ala Ser Thr Gly Tyr Val Val 845 850 855 Leu Trp Thr Leu Gly Gln Leu Val Ala Ser Thr Gly Tyr Val Val 845 850 855

Glu Pro Tyr Arg Lys Tyr Pro Thr Leu Leu Glu Val Leu Leu Asn 860 865 870 Glu Pro Tyr Arg Lys Tyr Pro Thr Leu Leu Glu Val Leu Leu Asn 860 865 870

Phe Leu Lys Thr Glu Gln Asn Gln Gly Thr Arg Arg Glu Ala Ile 875 880 885 Phe Leu Lys Thr Glu Gln Asn Gln Gly Thr Arg Arg Glu Ala Ile 875 880 885

Arg Val Leu Gly Leu Leu Gly Ala Leu Asp Pro Tyr Lys His Lys 890 895 900 Arg Val Leu Gly Leu Leu Gly Ala Leu Asp Pro Tyr Lys His Lys 890 895 900

Val Asn Ile Gly Met Ile Asp Gln Ser Arg Asp Ala Ser Ala Val 905 910 915 Val Asn Ile Gly Met Ile Asp Gln Ser Arg Asp Ala Ser Ala Val 905 910 915

Ser Leu Ser Glu Ser Lys Ser Ser Gln Asp Ser Ser Asp Tyr Ser 920 925 930 Be Leu Be Glu Be Lys Be Be Gln Asp Be Be Asp Tyr Be 920 925 930

Thr Ser Glu Met Leu Val Asn Met Gly Asn Leu Pro Leu Asp Glu 935 940 945 Thr Ser Glu Met Leu Val Asn Met Gly Asn Leu Pro Leu Asp Glu 935 940 945

Phe Tyr Pro Ala Val Ser Met Val Ala Leu Met Arg Ile Phe Arg 950 955 960 Phe Tyr Pro Wing Val Ser Met Val Wing Leu Met Arg Ile Phe Arg 950 955 960

Asp Gln Ser Leu Ser His His His Thr Met Val Val Gln Ala Ile 965 970 975 Asp Gln Ser Leu Ser His His Thr Met Val Val Gln Ala Ile 965 970 975

Thr Phe Ile Phe Lys Ser Leu Gly Leu Lys Cys Val Gln Phe Leu 980 985 990 Thr Phe Ile Phe Lys Ser Leu Gly Leu Lys Cys Val Gln Phe Leu 980 985 990

Pro Gln Val Met Pro Thr Phe Leu Asn Val Ile Arg Val Cys Asp 995 1000 1005 Pro Gln Val Met Pro Thr Phe Leu Asn Val Ile Arg Val Cys Asp 995 1000 1005

Gly Ala Ile Arg Glu Phe Leu Phe Gln Gln Leu Gly Met Leu Val 1010 1015 1020 Ser Phe Val Lys Ser His Ile Arg Pro Tyr Met Asp Glu Ile Val 1025 1030 1035 Gly Wing Ile Arg Glu Phe Leu Phe Gln Gln Leu Gly Met Leu Val 1010 1015 1020 Be Phe Val Lys Be His Ile Arg Pro Tyr Met Asp Glu Ile Val 1025 1030 1035

Thr Leu Met Arg Glu Phe Trp Val Met Asn Thr Ser Ile Gln Ser 1040 1045 1050 Thr Leu Met Arg Glu Phe Trp Val Met Asn Thr Ser Ile Gln Ser 1040 1045 1050

Thr Ile Ile Leu Leu Ile Glu Gln Ile Val Val Ala Leu Gly Gly 1055 1060 1065 Thr Ile Ile Leu Leu Ile Glu Gln Ile Val Val Ala Leu Gly Gly 1055 1060 1065

Glu Phe Lys Leu Tyr Leu Pro Gln Leu Ile Pro His Met Leu Arg 1070 1075 1080 Glu Phe Lys Leu Tyr Leu Pro Gln Leu Ile Pro His Met Leu Arg 1070 1075 1080

Val Phe Met His Asp Asn Ser Pro Gly Arg Ile Val Ser Ile Lys 1085 1090 1095 Val Phe Met His Asp Asn Ser Pro Gly Arg Ile Val Ser Ile Lys 1085 1090 1095

Leu Leu Ala Ala Ile Gln Leu Phe Gly Ala Asn Leu Asp Asp Tyr 1100 1105 1110 Leu Leu Wing Ile Gln Leu Phe Gly Wing Asn Leu Asp Asp Tyr 1100 1105 1110

Leu His Leu Leu Leu Pro Pro Ile Val Lys Leu Phe Asp Ala Pro 1115 1120 1125 Leu His Leu Leu Leu Pro Pro Ile Val Lys Leu Phe Asp Ala Pro 1115 1120 1125

Glu Ala Pro Leu Pro Ser Arg Lys Ala Ala Leu Glu Thr Val Asp 1130 1135 1140 Glu Ala Pro Leu Pro Ser Arg Lys Ala Ala Leu Glu Thr Val Asp 1130 1135 1140

Arg Leu Thr Glu Ser Leu Asp Phe Thr Asp Tyr Ala Ser Arg Ile 1145 1150 1155 Arg Leu Thr Glu Ser Leu Asp Phe Thr Asp Tyr Ala Ser Arg Ile 1145 1150 1155

Ile His Pro Ile Val Arg Thr Leu Asp Gln Ser Pro Glu Leu Arg 1160 1165 1170 Ile His Pro Ile Val Arg Thr Leu Asp Gln Ser Pro Glu Leu Arg 1160 1165 1170

Ser Thr Ala Met Asp Thr Leu Ser Ser Leu Val Phe Gln Leu Gly 1175 1180 1185 Be Thr Wing Met Asp Thr Leu Be Be Leu Val Phe Gln Leu Gly 1175 1180 1185

Lys Lys Tyr Gln Ile Phe Ile Pro Met Val Asn Lys Val Leu Val 1190 1195 1200 Lys Lys Tyr Gln Ile Phe Ile Pro Met Val Asn Lys Val Leu Val 1190 1195 1200

Arg His Arg Ile Asn His Gln Arg Tyr Asp Val Leu Ile Cys Arg 1205 1210 1215 Arg His Arg Ile Asn His Gln Arg Tyr Asp Val Leu Ile Cys Arg 1205 1210 1215

Ile Val Lys Gly Tyr Thr Leu Ala Asp Glu Glu Glu Asp Pro Leu 1220 1225 1230 Ile Val Lys Gly Tyr Thr Leu Wing Asp Glu Glu Glu Asp Pro Leu 1220 1225 1230

Ile Tyr Gln His Arg Met Leu Arg Ser Gly Gln Gly Asp Ala Leu 1235 1240 1245 Ile Tyr Gln His Arg Met Leu Arg Ser Gly Gln Gly Asp Ala Leu 1235 1240 1245

Ala Ser Gly Pro Val Glu Thr Gly Pro Met Lys Lys Leu His Val 1250 1255 1260 Wing Ser Gly Pro Val Glu Thr Gly Pro Met Lys Lys Leu His Val 1250 1255 1260

Ser Thr Ile Asn Leu Gln Lys Ala Thr Ala Trp Gly Ala Ala Arg 1265 1270 1275 Ser Thr Ile Asn Leu Gln Lys Wing Thr Wing Trp Gly Wing Wing Arg 1265 1270 1275

Arg Val Ser Lys Asp Asp Trp Leu Glu Trp Leu Arg Arg Leu Ser 1280 1285 1290 Arg Val Ser Lys Asp Asp Trp Leu Glu Trp Leu Arg Arg Leu Ser 1280 1285 1290

Leu Glu Leu Leu Lys Asp Ser Ser Ser Pro Ser Leu Arg Ser Cys 1295 1300 1305 Leu Glu Leu Leu Lys Asp Be Be Be Pro Be Ser Leu Arg Be Cys 1295 1300 1305

Trp Ala Leu Ala Gln Ala Tyr Asn Pro Met Ala Arg Asp Leu Phe 1310 1315 1320 Trp Wing Leu Wing Gln Wing Tyr Asn Pro Met Wing Arg Asp Leu Phe 1310 1315 1320

Asn Ala Ala Phe Val Ser Cys Trp Ser Glu Leu Asn Glu Asp Gln 1325 1330 1335 Asn Wing Phe Val Ser Cys Trp Ser Glu Leu Asn Glu Asp Gln 1325 1330 1335

Gln Asp Glu Leu Ile Arg Ser Ile Glu Leu Ala Leu Thr Ser Gln 1340 1345 1350 Gln Asp Glu Leu Ile Arg Ser Ile Glu Leu Ala Leu Thr Ser Gln 1340 1345 1350

Asp Ile Ala Glu Val Thr Gln Thr Leu Leu Asn Leu Ala Glu Phe Asp Ile Wing Glu Val Thr Gln Thr Leu Leu Asn Leu Wing Glu Phe

1355 1360 1355 1360

Met Glu His Ser Asp Lys Gly Pro Leu Pro Leu Arg Asp Asp Asn 1370 1375 1380 Met Glu His Ser Asp Lys Gly Pro Leu Pro Leu Arg Asp Asp Asn 1370 1375 1380

Gly Ile Val Leu Leu Gly Glu Arg Ala Ala Lys Cys Arg Ala Tyr 1385 1390 1395 Gly Ile Val Leu Leu Gly Glu Arg Wing Wing Lys Cys Arg Wing Tyr 1385 1390 1395

Ala Lys Ala Leu His Tyr Lys Glu Leu Glu Phe Gln Lys Gly Pro 1400 1405 1410 Ala Lys Ala Leu His Tyr Lys Glu Leu Glu Phe Gln Lys Gly Pro 1400 1405 1410

Thr Pro Ala Ile Leu Glu Ser Leu Ile Ser Ile Asn Asn Lys Leu 1415 1420 1425 Thr Pro Wing Ile Leu Glu Ser Leu Ile Ser Ile Asn Asn Lys Leu 1415 1420 1425

Gln Gln Pro Glu Ala Ala Ala Gly Val Leu Glu Tyr Ala Met Lys 1430 1435 1440 Gln Gln Pro Glu Wing Wing Gly Val Leu Glu Tyr Wing Met Lys 1430 1435 1440

His Phe Gly Glu Leu Glu Ile Gln Ala Thr Trp Tyr Glu Lys Leu 1445 1450 1455 His Phe Gly Glu Leu Glu Ile Gln Ala Thr Trp Tyr Glu Lys Leu 1445 1450 1455

His Glu Trp Glu Asp Ala Leu Val Ala Tyr Asp Lys Lys Met Asp 1460 1465 1470 His Glu Trp Glu Asp Ala Leu Val Ala Tyr Asp Lys Lys Met Asp 1460 1465 1470

Thr Asn Lys Asp Asp Pro Glu Leu Met Leu Gly Arg Met Arg Cys 1475 1480 1485 Thr Asn Lys Asp Asp Pro Glu Leu Met Leu Gly Arg Met Arg Cys 1475 1480 1485

Leu Glu Ala Leu Gly Glu Trp Gly Gln Leu His Gln Gln Cys Cys 1490 1495 1500 Leu Glu Wing Leu Gly Glu Trp Gly Gln Leu His Gln Gln Cys Cys 1490 1495 1500

Glu Lys Trp Thr Leu Val Asn Asp Glu Thr Gln Ala Lys Met Ala 1505 1510 1515 Glu Lys Trp Thr Leu Val Asn Asp Glu Thr Gln Ala Lys Met Ala 1505 1510 1515

Arg Met Ala Ala Ala Ala Ala Trp Gly Leu Gly Gln Trp Asp Ser 1520 1525 1530 Arg Met Wing Wing Wing Wing Trp Gly Leu Gly Gln Trp Asp Ser 1520 1525 1530

Met Glu Glu Tyr Thr Cys Met Ile Pro Arg Asp Thr His Asp Gly 1535 1540 1545 Met Glu Glu Tyr Thr Cys Met Ile Pro Arg Asp Thr His Asp Gly 1535 1540 1545

Ala Phe Tyr Arg Ala Val Leu Ala Leu His Gln Asp Leu Phe Ser 1550 1555 1560 Wing Phe Tyr Arg Wing Val Leu Wing Leu His Gln Asp Leu Phe Ser 1550 1555 1560

Leu Ala Gln Gln Cys Ile Asp Lys Ala Arg Asp Leu Leu Asp Ala 1565 1570 1575 Leu Wing Gln Gln Cys Ile Asp Lys Wing Arg Asp Leu Leu Asp Wing 1565 1570 1575

Glu Leu Thr Ala Met Ala Gly Glu Ser Tyr Ser Arg Ala Tyr Gly 1580 1585 1590 Glu Leu Thr Wing Met Wing Gly Glu Ser Tyr Ser Arg Wing Tyr Gly 1580 1585 1590

Ala Met Val Ser Cys His Met Leu Ser Glu Leu Glu Glu Val Ile 1595 1600 1605 Wing Met Val Ser Cys His Met Leu Ser Glu Leu Glu Glu Val Ile 1595 1600 1605

Gln Tyr Lys Leu Val Pro Glu Arg Arg Glu Ile Ile Arg Gln Ile 1610 1615 1620 Gln Tyr Lys Leu Val Pro Glu Arg Arg Glu Ile Ile Arg Gln Ile 1610 1615 1620

Trp Trp Glu Arg Leu Gln Gly Cys Gln Arg Ile Val Glu Asp Trp 1625 1630 1635 Trp Trp Glu Arg Leu Gln Gly Cys Gln Arg Ile Val Glu Asp Trp 1625 1630 1635

Gln Lys Ile Leu Met Val Arg Ser Leu Val Val Ser Pro His Glu 1640 1645 1650 Gln Lys Ile Leu Met Val Arg Ser Leu Val Val Ser Pro His Glu 1640 1645 1650

Asp Met Arg Thr Trp Leu Lys Tyr Ala Ser Leu Cys Gly Lys Ser 1655 1660 1665 Asp Met Arg Thr Trp Leu Lys Tyr Ala Ser Leu Cys Gly Lys Ser 1655 1660 1665

Gly Arg Leu Ala Leu Ala His Lys Thr Leu Val Leu Leu Leu Gly 1670 1675 1680 Gly Arg Leu Ala Leu Ala His Lys Thr Leu Val Leu Leu Leu Gly 1670 1675 1680

Val Asp Pro Ser Arg Gln Leu Asp His Pro Leu Pro Thr Val His 1685 1690 1695 Pro Gln Val Thr Tyr Ala Tyr Met Lys Asn Met Trp Lys Ser Ala 1700 1705 1710 Val Asp Pro Ser Arg Gln Leu Asp His Pro Leu Pro Thr Val His 1685 1690 1695 Pro Gln Val Thr Tyr Wing Tyr Met Lys Asn Met Trp Lys Ser Wing 1700 1705 1710

Arg Lys Ile Asp Ala Phe Gln His Met Gln His Phe Val Gln Thr 1715 1720 1725 Arg Lys Ile Asp Ala Phe Gln His Met Gln His Phe Val Gln Thr 1715 1720 1725

Met Gln Gln Gln Ala Gln His Ala Ile Ala Thr Glu Asp Gln Gln 1730 1735 1740 Met Gln Gln Gln Wing Gln His Wing Ile Wing Thr Glu Asp Gln Gln 1730 1735 1740

His Lys Gln Glu Leu His Lys Leu Met Ala Arg Cys Phe Leu Lys 1745 1750 1755 His Lys Gln Glu Leu His Lys Leu Met Ala Arg Cys Phe Leu Lys 1745 1750 1755

Leu Gly Glu Trp Gln Leu Asn Leu Gln Gly Ile Asn Glu Ser Thr 1760 1765 1770 Leu Gly Glu Trp Gln Leu Asn Leu Gln Gly Ile Asn Glu Ser Thr 1760 1765 1770

Ile Pro Lys Val Leu Gln Tyr Tyr Ser Ala Ala Thr Glu His Asp 1775 1780 1785 Ile Pro Lys Val Leu Gln Tyr Tyr Ser Ala Wing Thr Glu His Asp 1775 1780 1785

Arg Ser Trp Tyr Lys Ala Trp His Ala Trp Ala Val Met Asn Phe 1790 1795 1800 Arg Ser Trp Tyr Lys Wing Trp His Wing Trp Wing Val Met Asn Phe 1790 1795 1800

Glu Ala Val Leu His Tyr Lys His Gln Asn Gln Ala Arg Asp Glu 1805 1810 1815 Glu Ala Val Leu His Tyr Lys His Gln Asn Gln Ala Arg Asp Glu 1805 1810 1815

Lys Lys Lys Leu Arg His Ala Ser Gly Ala Asn Ile Thr Asn Ala 1820 1825 1830 Lys Lys Lys Leu Arg His Wing Being Gly Wing Asn Ile Thr Asn Wing 1820 1825 1830

Thr Thr Ala Ala Thr Thr Ala Ala Thr Ala Thr Thr Thr Ala Ser 1835 1840 1845 Thr Thr Wing Thr Wing Thr Wing Thr Wing Thr Wing Thr Thr Wing Ser 1835 1840 1845

Thr Glu Gly Ser Asn Ser Glu Ser Glu Ala Glu Ser Thr Glu Asn 1850 1855 1860 Thr Glu Gly Ser Asn Ser Glu Ser Glu Ala Glu Ser Thr Glu Asn 1850 1855 1860

Ser Pro Thr Pro Ser Pro Leu Gln Lys Lys Val Thr Glu Asp Leu 1865 1870 1875 Ser Pro Thr Pro Ser Pro Leu Gln Lys Lys Val Thr Glu Asp Leu 1865 1870 1875

Ser Lys Thr Leu Leu Met Tyr Thr Val Pro Ala Val Gln Gly Phe 1880 1885 1890 Ser Lys Thr Leu Leu Met Tyr Thr Val Pro Ala Val Gln Gly Phe 1880 1885 1890

Phe Arg Ser Ile Ser Leu Ser Arg Gly Asn Asn Leu Gln Asp Thr 1895 1900 1905 Phe Arg Ser Ile Ser Leu Ser Arg Gly Asn Asn Leu Gln Asp Thr 1895 1900 1905

Leu Arg Val Leu Thr Leu Trp Phe Asp Tyr Gly His Trp Pro Asp 1910 1915 1920 Leu Arg Val Leu Thr Leu Trp Phe Asp Tyr Gly His Trp Pro Asp 1910 1915 1920

Val Asn Glu Ala Leu Val Glu Gly Val Lys Ala Ile Gln Ile Asp 1925 1930 1935 Val Asn Glu Wing Leu Val Glu Gly Val Lys Wing Ile Gln Ile Asp 1925 1930 1935

Thr Trp Leu Gln Val Ile Pro Gln Leu Ile Ala Arg Ile Asp Thr 1940 1945 1950 Thr Trp Leu Gln Val Ile Pro Gln Leu Ile Wing Arg Ile Asp Thr 1940 1945 1950

Pro Arg Pro Leu Val Gly Arg Leu Ile His Gln Leu Leu Thr Asp 1955 1960 1965 Pro Arg Pro Leu Val Gly Arg Leu Ile His Gln Leu Leu Thr Asp 1955 1960 1965

Ile Gly Arg Tyr His Pro Gln Ala Leu Ile Tyr Pro Leu Thr Val 1970 1975 1980 Ile Gly Arg Tyr His Pro Gln Ala Leu Ile Tyr Pro Leu Thr Val 1970 1975 1980

Ala Ser Lys Ser Thr Thr Thr Ala Arg His Asn Ala Ala Asn Lys 1985 1990 1995 Ala Ser Lys Ser Thr Thr Thr Ala Arg His Asn Ala Ala Asn Lys 1985 1990 1995

Ile Leu Lys Asn Met Cys Glu His Ser Asn Thr Leu Val Gln Gln 2000 2005 2010 Ile Leu Lys Asn Met Cys Glu His Ser Asn Thr Leu Val Gln Gln 2000 2005 2010

Ala Met Met Val Ser Glu Glu Leu Ile Arg Val Ala Ile Leu Trp 2015 2020 2025 Wing Met Met Val Ser Glu Glu Leu Ile Arg Val Wing Ile Leu Trp 2015 2020 2025

His Glu Met Trp His Glu Gly Leu Glu Glu Ala Ser Arg Leu Tyr 2030 2035 2040 Phe Gly Glu Arg Asn Val Lys Gly Met Phe Glu Val Leu Glu Pro 2045 2050 2055 His Glu Met Trp His Glu Gly Leu Glu Glu Ala Ser Arg Leu Tyr 2030 2035 2040 Phe Gly Glu Arg Asn Val Lys Gly Met Phe Glu Val Leu Glu Pro 2045 2050 2055

Leu His Ala Met Met Glu Arg Gly Pro Gln Thr Leu Lys Glu Thr 2060 2065 2070 Leu His Wing Met Met Glu Arg Gly Pro Gln Thr Leu Lys Glu Thr 2060 2065 2070

Ser Phe Asn Gln Ala Tyr Gly Arg Asp Leu Met Glu Ala Gln Glu 2075 2080 2085 Ser Phe Asn Gln Ala Tyr Gly Arg Asp Leu Met Glu Ala Gln Glu 2075 2080 2085

Trp Cys Arg Lys Tyr Met Lys Ser Gly Asn Val Lys Asp Leu Thr 2090 2095 2100 Trp Cys Arg Lys Tyr Met Lys Ser Gly Asn Val Lys Asp Leu Thr 2090 2095 2100

Gln Ala Trp Asp Leu Tyr Tyr His Val Phe Arg Arg Ile Ser Lys 2105 2110 2115 Gln Wing Trp Asp Leu Tyr Tyr His Val Phe Arg Arg Ile Ser Lys 2105 2110 2115

Gln Leu Pro Gln Leu Thr Ser Leu Glu Leu Gln Tyr Val Ser Pro 2120 2125 2130 Gln Leu Pro Gln Leu Thr Ser Leu Glu Leu Gln Tyr Val Ser Pro 2120 2125 2130

Lys Leu Leu Met Cys Arg Asp Leu Glu Leu Ala Val Pro Gly Thr 2135 2140 2145 Lys Leu Leu Met Cys Arg Asp Leu Glu Leu Ala Val Pro Gly Thr 2135 2140 2145

Tyr Asp Pro Asn Gln Pro Ile Ile Arg Ile Gln Ser Ile Ala Pro 2150 2155 2160 Tyr Asp Pro Asn Gln Pro Ile Ile Arg Ile Gln Ser Ile Ala Pro 2150 2155 2160

Ser Leu Gln Val Ile Thr Ser Lys Gln Arg Pro Arg Lys Leu Thr 2165 2170 2175 Ser Leu Gln Val Ile Thr Ser Lys Gln Arg Pro Arg Lys Leu Thr 2165 2170 2175

Leu Met Gly Ser Asn Gly His Glu Phe Val Phe Leu Leu Lys Gly 2180 2185 2190 Leu Met Gly Ser Asn Gly His Glu Phe Val Phe Leu Leu Lys Gly 2180 2185 2190

His Glu Asp Leu Arg Gln Asp Glu Arg Val Met Gln Leu Phe Gly 2195 2200 2205 His Glu Asp Leu Arg Gln Asp Glu Arg Val Met Gln Leu Phe Gly 2195 2200 2205

Leu Val Asn Thr Leu Leu Ala Asn Asp Pro Thr Ser Leu Arg Lys 2210 2215 2220 Leu Val Asn Thr Leu Leu Ala Asn Asp Pro Thr Ser Leu Arg Lys 2210 2215 2220

Asn Leu Ser Ile Gln Arg Tyr Ala Val Ile Pro Leu Ser Thr Asn 2225 2230 2235 Asn Leu Ser Ile Gln Arg Tyr Ala Val Ile Pro Leu Ser Thr Asn 2225 2230 2235

Ser Gly Leu Ile Gly Trp Val Pro His Cys Asp Thr Leu His Ala 2240 2245 2250 Ser Gly Leu Ile Gly Trp Val Pro His Cys Asp Thr Leu His Ala 2240 2245 2250

Leu Ile Arg Asp Tyr Arg Glu Lys Lys Lys Ile Leu Leu Asn Ile 2255 2260 2265 Leu Ile Arg Asp Tyr Arg Glu Lys Lys Lys Ile Leu Leu Asn Ile 2255 2260 2265

Glu His Arg Ile Met Leu Arg Met Ala Pro Asp Tyr Asp His Leu 2270 2275 2280 Glu His Arg Ile Met Leu Arg Met Ala Pro Asp Tyr Asp His Leu 2270 2275 2280

Thr Leu Met Gln Lys Val Glu Val Phe Glu His Ala Val Asn Asn 2285 2290 2295 Thr Leu Met Gln Lys Val Glu Val Phe Glu His Ala Val Asn Asn 2285 2290 2295

Thr Ala Gly Asp Asp Leu Ala Lys Leu Leu Trp Leu Lys Ser Pro 2300 2305 2310 Thr Wing Gly Asp Asp Leu Wing Lys Leu Leu Trp Leu Lys Ser Pro 2300 2305 2310

Ser Ser Glu Val Trp Phe Asp Arg Arg Thr Asn Tyr Thr Arg Ser 2315 2320 2325 Be Ser Glu Val Trp Phe Asp Arg Arg Thr Asn Tyr Thr Arg Ser 2315 2320 2325

Leu Ala Val Met Ser Met Val Gly Tyr Ile Leu Gly Leu Gly Asp 2330 2335 2340 Leu Wing Val Met Ser Met Val Gly Tyr Ile Leu Gly Leu Gly Asp 2330 2335 2340

Arg His Pro Ser Asn Leu Met Leu Asp Arg Leu Ser Gly Lys Ile 2345 2350 2355 Arg His Pro Ser Asn Leu Met Leu Asp Arg Leu Ser Gly Lys Ile 2345 2350 2355

Leu His Ile Asp Phe Gly Asp Cys Phe Glu Val Ala Met Thr Arg 2360 2365 2370 Leu His Ile Asp Phe Gly Asp Cys Phe Glu Val Wing Met Thr Arg 2360 2365 2370

Glu Lys Phe Pro Glu Lys Ile Pro Phe Arg Leu Thr Arg Met Leu Glu Lys Phe Pro Glu Lys Ile Pro Phe Arg Leu Thr Arg Met Leu

2375 2380 2385 2375 2380 2385

Thr Asn Ala Met Glu Val Thr Gly Leu Asp Gly Asn Tyr Arg Ile 2390 2395 2400 Thr Asn Wing Met Glu Val Thr Gly Leu Asp Gly Asn Tyr Arg Ile 2390 2395 2400

Thr Cys His Thr Val Met Glu Val Leu Arg Glu His Lys Asp Ser 2405 2410 2415 Thr Cys His Thr Val Met Glu Val Leu Arg Glu His Lys Asp Ser 2405 2410 2415

Val Met Ala Val Leu Glu Ala Phe Val Tyr Asp Pro Leu Leu Asn 2420 2425 2430 Val Met Wing Val Leu Glu Wing Phe Val Tyr Asp Pro Leu Leu Asn 2420 2425 2430

Trp Arg Leu Met Asp Thr Asn Thr Lys Gly Asn Lys Arg Ser Arg 2435 2440 2445 Trp Arg Leu Met Asp Thr Asn Thr Lys Gly Asn Lys Arg Ser Arg 2435 2440 2445

Thr Arg Thr Asp Ser Tyr Ser Ala Gly Gln Ser Val Glu Ile Leu 2450 2455 2460 Thr Arg Thr Asp Ser Tyr Ser Ala Gly Gln Ser Val Glu Ile Leu 2450 2455 2460

Asp Gly Val Glu Leu Gly Glu Pro Ala His Lys Lys Thr Gly Thr 2465 2470 2475 Asp Gly Val Glu Leu Gly Glu Pro Ala His Lys Lys Thr Gly Thr 2465 2470 2475

Thr Val Pro Glu Ser Ile His Ser Phe Ile Gly Asp Gly Leu Val 2480 2485 2490 Thr Val Pro Glu Ser Ile His Ser Phe Ile Gly Asp Gly Leu Val 2480 2485 2490

Lys Pro Glu Ala Leu Asn Lys Lys Ala Ile Gln Ile Ile Asn Arg 2495 2500 2505 Lys Pro Glu Wing Leu Asn Lys Lys Wing Ile Gln Ile Ile Asn Arg 2495 2500 2505

Val Arg Asp Lys Leu Thr Gly Arg Asp Phe Ser His Asp Asp Thr 2510 2515 2520 Val Arg Asp Lys Leu Thr Gly Arg Asp Phe Ser His Asp Asp Thr 2510 2515 2520

Leu Asp Val Pro Thr Gln Val Glu Leu Leu Ile Lys Gln Ala Thr 2525 2530 2535 Leu Asp Val Pro Thr Gln Val Glu Leu Leu Ile Lys Gln Ala Thr 2525 2530 2535

Ser His Glu Asn Leu Cys Gln Cys Tyr Ile Gly Trp Cys Pro Phe 2540 2545 2550 Ser His Glu Asn Leu Cys Gln Cys Tyr Ile Gly Trp Cys Pro Phe 2540 2545 2550

Trp Trp

<210> 46 <210> 46

<211> 1356 <211> 1356

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 46 Met Gln Ser Lys Val Leu Leu Ala Val Ala Leu Trp Leu Cys Val 1 5 10 15 <400> 46 Met Gln Ser Lys Val Leu Leu Val Wing Leu Trp Leu Cys Val 1 5 10 15

Glu Thr Arg Ala Ala Ser Val Gly Leu Pro Ser Val Ser Leu Asp 20 25 30 Glu Thr Arg Wing Ser Ser Val Gly Leu Pro Ser Val Ser Leu Asp 20 25 30

Leu Pro Arg Leu Ser Ile Gln Lys Asp Ile Leu Thr Ile Lys Ala 35 40 45 Leu Pro Arg Leu Ser Ile Gln Lys Asp Ile Leu Thr Ile Lys Wing 35 40 45

Asn Thr Thr Leu Gln Ile Thr Cys Arg Gly Gln Arg Asp Leu Asp 50 55 60 Asn Thr Thr Leu Gln Ile Thr Cys Arg Gly Gln Arg Asp Leu Asp 50 55 60

Trp Leu Trp Pro Asn Asn Gln Ser Gly Ser Glu Gln Arg Val Glu 65 70 75 Trp Leu Trp Pro Asn Asn Gln Ser Gly Ser Glu Gln Arg Val Glu 65 70 75

Val Thr Glu Cys Ser Asp Gly Leu Phe Cys Lys Thr Leu Thr Ile 80 85 90 Val Thr Glu Cys Ser Asp Gly Leu Phe Cys Lys Thr Leu Thr Ile 80 85 90

Pro Lys Val Ile Gly Asn Asp Thr Gly Ala Tyr Lys Cys Phe Tyr 95 100 105 Pro Lys Val Ile Gly Asn Asp Thr Gly Ala Tyr Lys Cys Phe Tyr 95 100 105

Arg Glu Thr Asp Leu Ala Ser Val Ile Tyr Val Tyr Val Gln Asp 110 115 120 Tyr Arg Ser Pro Phe Ile Ala Ser Val Ser Asp Gln His Gly Val 125 130 Arg Glu Thr Asp Leu Ala Ser Val Ile Tyr Val Tyr Val Gln Asp 110 115 120 Tyr Arg Ser Pro Phe Ile Ala Ser Val Ser Asp Gln His Gly Val 125 130

Val Tyr Ile Thr Glu Asn Lys Asn Lys Thr Val Val Ile Pro Cys 140 145 150 Val Tyr Ile Thr Glu Asn Lys Asn Lys Thr Val Val Ile Pro Cys 140 145 150

Leu Gly Ser Ile Ser Asn Leu Asn Val Ser Leu Cys Ala Arg Tyr 155 160 165 Leu Gly Ser Ile Ser Asn Leu Asn Val Ser Leu Cys Ala Arg Tyr 155 160 165

Pro Glu Lys Arg Phe Val Pro Asp Gly Asn Arg Ile Ser Trp Asp 170 175 180 Pro Glu Lys Arg Phe Val Pro Asp Gly Asn Arg Ile Ser Trp Asp 170 175 180

Ser Lys Lys Gly Phe Thr Ile Pro Ser Tyr Met Ile Ser Tyr Ala 185 190 195 Ser Lys Lys Gly Phe Thr Ile Pro Ser Tyr Met Ile Ser Tyr Ala 185 190 195

Gly Met Val Phe Cys Glu Ala Lys Ile Asn Asp Glu Ser Tyr Gln 200 205 210 Gly Met Val Phe Cys Glu Ala Lys Ile Asn Asp Glu Ser Tyr Gln 200 205 210

Ser Ile Met Tyr Ile Val Val Val Val Gly Tyr Arg Ile Tyr Asp 215 220 225 Be Ile Met Tyr Ile Val Val Val Val Gly Tyr Arg Ile Tyr Asp 215 220 225

Val Val Leu Ser Pro Ser His Gly Ile Glu Leu Ser Val Gly Glu 230 235 240 Val Val Leu Ser Pro Ser His Gly Ile Glu Leu Ser Val Gly Glu 230 235 240

Lys Leu Val Leu Asn Cys Thr Ala Arg Thr Glu Leu Asn Val Gly 245 250 255 Lys Leu Val Leu Asn Cys Thr Wing Arg Thr Glu Leu Asn Val Gly 245 250 255

Ile Asp Phe Asn Trp Glu Tyr Pro Ser Ser Lys His Gln His Lys 260 265 270 Ile Asp Phe Asn Trp Glu Tyr Pro Ser Ser Lys His Gln His Lys 260 265 270

Lys Leu Val Asn Arg Asp Leu Lys Thr Gln Ser Gly Ser Glu Met 275 280 285 Lys Leu Val Asn Arg Asp Leu Lys Thr Gln Ser Gly Ser Glu Met 275 280 285

Lys Lys Phe Leu Ser Thr Leu Thr Ile Asp Gly Val Thr Arg Ser 290 295 300 Lys Lys Phe Leu Ser Thr Leu Thr Ile Asp Gly Val Thr Arg Ser 290 295 300

Asp Gln Gly Leu Tyr Thr Cys Ala Ala Ser Ser Gly Leu Met Thr 305 310 315 Asp Gln Gly Leu Tyr Thr Cys Wing Wing Be Being Gly Leu Met Thr 305 310 315

Lys Lys Asn Ser Thr Phe Val Arg Val His Glu Lys Pro Phe Val 320 325 330 Lys Lys Asn Ser Thr Phe Val Arg Val His Glu Lys Pro Phe Val 320 325 330

Ala Phe Gly Ser Gly Met Glu Ser Leu Val Glu Ala Thr Val Gly 335 340 345 Wing Phe Gly Ser Gly Met Glu Ser Leu Val Glu Wing Thr Val Gly 335 340 345

Glu Arg Val Arg Ile Pro Ala Lys Tyr Leu Gly Tyr Pro Pro Pro 350 355 360 Glu Arg Val Arg Ile Pro Ala Lys Tyr Leu Gly Tyr Pro Pro 350 355 360

Glu Ile Lys Trp Tyr Lys Asn Gly Ile Pro Leu Glu Ser Asn His 365 370 375 Glu Ile Lys Trp Tyr Lys Asn Gly Ile Pro Leu Glu Ser Asn His 365 370 375

Thr Ile Lys Ala Gly His Val Leu Thr Ile Met Glu Val Ser Glu 380 385 390 Thr Ile Lys Ala Gly His Val Leu Thr Ile Met Glu Val Ser Glu 380 385 390

Arg Asp Thr Gly Asn Tyr Thr Val Ile Leu Thr Asn Pro Ile Ser 395 400 405 Arg Asp Thr Gly Asn Tyr Thr Val Ile Leu Thr Asn Pro Ile Ser 395 400 405

Lys Glu Lys Gln Ser His Val Val Ser Leu Val Val Tyr Val Pro 410 415 420 Lys Glu Lys Gln Ser His Val Val Ser Leu Val Val Tyr Val Pro 410 415 420

Pro Gln Ile Gly Glu Lys Ser Leu Ile Ser Pro Val Asp Ser Tyr 425 430 435 Pro Gln Ile Gly Glu Lys Ser Leu Ile Ser Pro Val Asp Ser Tyr 425 430 435

Gln Tyr Gly Thr Thr Gln Thr Leu Thr Cys Thr Val Tyr Ala Ile 440 445 450 Gln Tyr Gly Thr Thr Gln Thr Leu Thr Cys Thr Val Tyr Ile 440 445 450

Pro Pro Pro His His Ile His Trp Tyr Trp Gln Leu Glu Glu Glu 455 460 Pro Pro Pro His His Ile His Trp Tyr Trp Gln Leu Glu Glu Glu 455 460

Cys Ala Asn Glu Pro Ser Gln Ala Val Ser Val Thr Asn Pro Tyr 470 475 Cys Ala Asn Glu Pro Ser Gln Ala Val Ser Val Thr Asn Pro Tyr 470 475

Pro Cys Glu Glu Trp Arg Ser Val Glu Asp Phe Gln Gly Gly Asn 485 490 495 Pro Cys Glu Glu Trp Arg Ser Val Glu Asp Phe Gln Gly Gly Asn 485 490 495

Lys Ile Glu Val Asn Lys Asn Gln Phe Ala Leu Ile Glu Gly Lys 500 505 510 Lys Ile Glu Val Asn Lys Asn Gln Phe Ala Leu Ile Glu Gly Lys 500 505 510

Asn Lys Thr Val Ser Thr Leu Val Ile Gln Ala Ala Asn Val Ser 515 520 525 Asn Lys Thr Val Ser Thr Leu Val Ile Gln Wing Asn Val Ser 515 520 525

Ala Leu Tyr Lys Cys Glu Ala Val Asn Lys Val Gly Arg Gly Glu 530 535 540 Wing Leu Tyr Lys Cys Glu Wing Val Asn Lys Val Gly Arg Gly Glu 530 535 540

Arg Val Ile Ser Phe His Val Thr Arg Gly Pro Glu Ile Thr Leu 545 550 555 Arg Val Ile Ser Phe His Val Thr Arg Gly Pro Glu Ile Thr Leu 545 550 555

Gln Pro Asp Met Gln Pro Thr Glu Gln Glu Ser Val Ser Leu Trp 560 565 570 Gln Pro Asp Met Gln Pro Thr Glu Gln Glu Ser Val Ser Leu Trp 560 565 570

Cys Thr Ala Asp Arg Ser Thr Phe Glu Asn Leu Thr Trp Tyr Lys 575 580 585 Cys Thr Wing Asp Arg Ser Thr Phe Glu Asn Leu Thr Trp Tyr Lys 575 580 585

Leu Gly Pro Gln Pro Leu Pro Ile His Val Gly Glu Leu Pro Thr 590 595 600 Leu Gly Pro Gln Pro Leu Pro Ile His Val Gly Glu Leu Pro Thr 590 595 600

Pro Val Cys Lys Asn Leu Asp Thr Leu Trp Lys Leu Asn Ala Thr 605 610 615 Pro Val Cys Lys Asn Leu Asp Thr Leu Trp Lys Leu Asn Ala Thr 605 610 615

Met Phe Ser Asn Ser Thr Asn Asp Ile Leu Ile Met Glu Leu Lys 620 625 630 Met Phe Ser Asn Ser Thr Asn Asp Ile Leu Ile Met Glu Leu Lys 620 625 630

Asn Ala Ser Leu Gln Asp Gln Gly Asp Tyr Val Cys Leu Ala Gln 635 640 645 Asn Wing Ser Leu Gln Asp Gln Gly Asp Tyr Val Cys Leu Wing Gln 635 640 645

Asp Arg Lys Thr Lys Lys Arg His Cys Val Val Arg Gln Leu Thr 650 655 660 Asp Arg Lys Thr Lys Lys Arg His Cys Val Val Arg Gln Leu Thr 650 655 660

Val Leu Glu Arg Val Ala Pro Thr Ile Thr Gly Asn Leu Glu Asn 665 670 675 Val Leu Glu Arg Val Ala Pro Thr Ile Thr Gly Asn Leu Glu Asn 665 670 675

Gln Thr Thr Ser Ile Gly Glu Ser Ile Glu Val Ser Cys Thr Ala 680 685 690 Gln Thr Thr Ser Ile Gly Glu Ser Ile Glu Val Ser Cys Thr Ala 680 685 690

Ser Gly Asn Pro Pro Pro Gln Ile Met Trp Phe Lys Asp Asn Glu 695 700 705 Ser Gly Asn Pro Pro Pro Gln Ile Met Trp Phe Lys Asp Asn Glu 695 700 705

Thr Leu Val Glu Asp Ser Gly Ile Val Leu Lys Asp Gly Asn Arg 710 715 720 Thr Leu Val Glu Asp Ser Gly Ile Val Leu Lys Asp Gly Asn Arg 710 715 720

Asn Leu Thr Ile Arg Arg Val Arg Lys Glu Asp Glu Gly Leu Tyr 725 730 735 Asn Leu Thr Ile Arg Arg Val Arg Lys Glu Asp Glu Gly Leu Tyr 725 730 735

Thr Cys Gln Ala Cys Ser Val Leu Gly Cys Ala Lys Val Glu Ala 740 745 750 Thr Cys Gln Ala Cys Ser Val Leu Gly Cys Ala Lys Val Glu Ala 740 745 750

Phe Phe Ile Ile Glu Gly Ala Gln Glu Lys Thr Asn Leu Glu Ile 755 760 765 Phe Phe Ile Ile Glu Gly Ala Gln Glu Lys Thr Asn Leu Glu Ile 755 760 765

Ile Ile Leu Val Gly Thr Ala Val Ile Ala Met Phe Phe Trp Leu 770 775 780 Ile Ile Leu Val Gly Thr Wing Val Ile Wing Met Phe Phe Trp Leu 770 775 780

Leu Leu Val Ile Ile Leu Arg Thr Val Lys Arg Ala Asn Gly Gly 785 790 795 Leu Leu Val Ile Ile Leu Arg Thr Val Lys Arg Wing Asn Gly Gly 785 790 795

Glu Leu Lys Thr Gly Tyr Leu Ser Ile Val Met Asp Pro Asp Glu Glu Leu Lys Thr Gly Tyr Leu Ser Ile Val Met Asp Pro Asp Glu

800 805 800 805

Leu Pro Leu Asp Glu His Cys Glu Arg Leu Pro Tyr Asp Ala Ser 815 820 825 Leu Pro Leu Asp Glu His Cys Glu Arg Leu Pro Tyr Asp Ala Ser 815 820 825

Lys Trp Glu Phe Pro Arg Asp Arg Leu Lys Leu Gly Lys Pro Leu 830 835 840 Lys Trp Glu Phe Pro Arg Asp Arg Leu Lys Leu Gly Lys Pro Leu 830 835 840

Gly Arg Gly Ala Phe Gly Gln Val Ile Glu Ala Asp Ala Phe Gly 845 850 855 Gly Arg Gly Wing Phe Gly Gln Val Ile Glu Wing Asp Wing Phe Gly 845 850 855

Ile Asp Lys Thr Ala Thr Cys Arg Thr Val Ala Val Lys Met Leu 860 865 870 Ile Asp Lys Thr Ala Thr Cys Arg Thr Val Ala Val Lys Met Leu 860 865 870

Lys Glu Gly Ala Thr His Ser Glu His Arg Ala Leu Met Ser Glu 875 880 885 Lys Glu Gly Ala Thr His Ser Glu His Arg Ala Leu Met Ser Glu 875 880 885

Leu Lys Ile Leu Ile His Ile Gly His His Leu Asn Val Val Asn 890 895 900 Leu Lys Ile Leu Ile His Ile Gly His His Leu Asn Val Val Asn 890 895 900

Leu Leu Gly Ala Cys Thr Lys Pro Gly Gly Pro Leu Met Val Ile 905 910 915 Leu Leu Gly Ala Cys Thr Lys Pro Gly Gly Pro Leu Met Val Ile 905 910 915

Val Glu Phe Cys Lys Phe Gly Asn Leu Ser Thr Tyr Leu Arg Ser 920 925 930 Val Glu Phe Cys Lys Phe Gly Asn Leu Ser Thr Tyr Leu Arg Ser 920 925 930

Lys Arg Asn Glu Phe Val Pro Tyr Lys Thr Lys Gly Ala Arg Phe 935 940 945 Lys Arg Asn Glu Phe Val Pro Tyr Lys Thr Lys Gly Ala Arg Phe 935 940 945

Arg Gln Gly Lys Asp Tyr Val Gly Ala Ile Pro Val Asp Leu Lys 950 955 960 Arg Gln Gly Lys Asp Tyr Val Gly Wing Ile Pro Val Asp Leu Lys 950 955 960

Arg Arg Leu Asp Ser Ile Thr Ser Ser Gln Ser Ser Ala Ser Ser 965 970 975 Arg Arg Leu Asp Be Ile Thr Be Be Gln Be Be Wing Be Be 965 970 975

Gly Phe Val Glu Glu Lys Ser Leu Ser Asp Val Glu Glu Glu Glu 980 985 990 Gly Phe Val Glu Glu Lys Ser Leu Ser Asp Val Glu Glu Glu Glu 980 985 990

Ala Pro Glu Asp Leu Tyr Lys Asp Phe Leu Thr Leu Glu His Leu 995 1000 1005 Pro Wing Glu Asp Leu Tyr Lys Asp Phe Leu Thr Leu Glu His Leu 995 1000 1005

Ile Cys Tyr Ser Phe Gln Val Ala Lys Gly Met Glu Phe Leu Ala 1010 1015 1020 Ile Cys Tyr Ser Phe Gln Val Ala Lys Gly Met Glu Phe Leu Ala 1010 1015 1020

Ser Arg Lys Cys Ile His Arg Asp Leu Ala Ala Arg Asn Ile Leu 1025 1030 1035 Ser Arg Lys Cys Ile His Arg Asp Leu Wing Wing Arg Asn Ile Leu 1025 1030 1035

Leu Ser Glu Lys Asn Val Val Lys Ile Cys Asp Phe Gly Leu Ala 1040 1045 1050 Leu Ser Glu Lys Asn Val Val Lys Ile Cys Asp Phe Gly Leu Ala 1040 1045 1050

Arg Asp Ile Tyr Lys Asp Pro Asp Tyr Val Arg Lys Gly Asp Ala 1055 1060 1065 Arg Asp Ile Tyr Lys Asp Pro Asp Tyr Val Arg Lys Gly Asp Wing 1055 1060 1065

Arg Leu Pro Leu Lys Trp Met Ala Pro Glu Thr Ile Phe Asp Arg 1070 1075 1080 Arg Leu Pro Leu Lys Trp Met Wing Pro Glu Thr Ile Phe Asp Arg 1070 1075 1080

Val Tyr Thr Ile Gln Ser Asp Val Trp Ser Phe Gly Val Leu Leu 1085 1090 1095 Val Tyr Thr Ile Gln Ser Asp Val Trp Ser Phe Gly Val Leu Leu 1085 1090 1095

Trp Glu Ile Phe Ser Leu Gly Ala Ser Pro Tyr Pro Gly Val Lys 1100 1105 1110 Trp Glu Ile Phe Ser Leu Gly Ala Ser Pro Tyr Pro Gly Val Lys 1100 1105 1110

Ile Asp Glu Glu Phe Cys Arg Arg Leu Lys Glu Gly Thr Arg Met 1115 1120 1125 Ile Asp Glu Glu Phe Cys Arg Arg Leu Lys Glu Gly Thr Arg Met 1115 1120 1125

Arg Ala Pro Asp Tyr Thr Thr Pro Glu Met Tyr Gln Thr Met Leu 1130 1135 1140 Arg Ala Pro Asp Tyr Thr Thr Pro Glu Met Tyr Gln Thr Met Leu 1130 1135 1140

Asp Cys Trp His Gly Glu Pro Ser Gln Arg Pro Thr Phe Ser Glu 1145 1150 1155 Asp Cys Trp His Gly Glu Pro Ser Gln Arg Pro Thr Phe Ser Glu 1145 1150 1155

Leu Val Glu His Leu Gly Asn Leu Leu Gln Ala Asn Ala Gln Gln 1160 1165 1170 Leu Val Glu His Leu Gly Asn Leu Leu Gln Wing Asn Wing Gln Gln 1160 1165 1170

Asp Gly Lys Asp Tyr Ile Val Leu Pro Ile Ser Glu Thr Leu Ser 1175 1180 1185 Asp Gly Lys Asp Tyr Ile Val Leu Pro Ile Ser Glu Thr Leu Ser 1175 1180 1185

Met Glu Glu Asp Ser Gly Leu Ser Leu Pro Thr Ser Pro Val Ser 1190 1195 1200 Met Glu Glu Asp Ser Gly Leu Ser Leu Pro Thr Ser Pro Val Ser 1190 1195 1200

Cys Met Glu Glu Glu Glu Val Cys Asp Pro Lys Phe His Tyr Asp 1205 1210 1215 Cys Met Glu Glu Glu Glu Val Cys Asp Pro Lys Phe His Tyr Asp 1205 1210 1215

Asn Thr Ala Gly Ile Ser Gln Tyr Leu Gln Asn Ser Lys Arg Lys 1220 1225 1230 Asn Thr Wing Gly Ile Ser Gln Tyr Leu Gln Asn Ser Lys Arg Lys 1220 1225 1230

Ser Arg Pro Val Ser Val Lys Thr Phe Glu Asp Ile Pro Leu Glu 1235 1240 1245 Ser Arg Pro Val Ser Val Lys Thr Phe Glu Asp Ile Pro Leu Glu 1235 1240 1245

Glu Pro Glu Val Lys Val Ile Pro Asp Asp Asn Gln Thr Asp Ser 1250 1255 1260 Glu Pro Glu Val Lys Val Ile Pro Asp Asp Asn Gln Thr Asp Ser 1250 1255 1260

Gly Met Val Leu Ala Ser Glu Glu Leu Lys Thr Leu Glu Asp Arg 1265 1270 1275 Gly Met Val Leu Wing Ser Glu Glu Leu Lys Thr Leu Glu Asp Arg 1265 1270 1275

Thr Lys Leu Ser Pro Ser Phe Gly Gly Met Val Pro Ser Lys Ser 1280 1285 1290 Thr Lys Leu Ser Pro Ser Phe Gly Gly Met Val Pro Ser Lys Ser 1280 1285 1290

Arg Glu Ser Val Ala Ser Glu Gly Ser Asn Gln Thr Ser Gly Tyr 1295 1300 1305 Arg Glu Ser Val Ala Ser Glu Gly Ser Asn Gln Thr Ser Gly Tyr 1295 1300 1305

Gln Ser Gly Tyr His Ser Asp Asp Thr Asp Thr Thr Val Tyr Ser 1310 1315 1320 Gln Ser Gly Tyr His Ser Asp Asp Thr Asp Thr Thr Val Tyr Ser 1310 1315 1320

Ser Glu Glu Ala Glu Leu Leu Lys Leu Ile Glu Ile Gly Val Gln 1325 1330 1335 Ser Glu Glu Ala Glu Leu Leu Lys Leu Ile Glu Ile Gly Val Gln 1325 1330 1335

Thr Gly Ser Thr Ala Gln Ile Leu Gln Pro Asp Ser Gly Thr Thr 1340 1345 1350 Thr Gly Ser Thr Wing Gln Ile Leu Gln Pro Asp Ser Gly Thr Thr 1340 1345 1350

Leu Ser Ser Pro Pro Val 1355 Leu Ser Ser Pro Pro Val 1355

<210> 47 <210> 47

<211> 1408 <211> 1408

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 47 Met Lys Ala Pro Ala Val Leu Ala Pro Gly Ile Leu Val Leu Leu 1 5 10 15 <400> 47 Met Lys Pro Wing Val Leu Wing Pro Gly Ile Leu Val Leu Leu 1 5 10 15

Phe Thr Leu Val Gln Arg Ser Asn Gly Glu Cys Lys Glu Ala Leu 20 25 30 Phe Thr Leu Val Gln Arg Ser Asn Gly Glu Cys Lys Glu Ala Leu 20 25 30

Ala Lys Ser Glu Met Asn Val Asn Met Lys Tyr Gln Leu Pro Asn 35 40 45 Wing Lys Ser Glu Met Asn Val Asn Met Lys Tyr Gln Leu Pro Asn 35 40 45

Phe Thr Ala Glu Thr Pro Ile Gln Asn Val Ile Leu His Glu His 50 55 60 Phe Thr Wing Glu Thr Pro Ile Gln Asn Val Ile Leu His Glu His 50 55 60

His Ile Phe Leu Gly Ala Thr Asn Tyr Ile Tyr Val Leu Asn Glu 65 70 75 His Ile Phe Leu Gly Ala Thr Asn Tyr Ile Tyr Val Leu Asn Glu 65 70 75

Glu Asp Leu Gln Lys Val Ala Glu Tyr Lys Thr Gly Pro Val Leu 80 85 90 Glu His Pro Asp Cys Phe Pro Cys Gln Asp Cys Ser Ser Lys Ala 95 100 Glu Asp Leu Gln Lys Val Wing Glu Tyr Lys Thr Gly Pro Val Leu 80 85 90 Glu His Pro Asp Cys Phe Pro Cys Gln Asp Cys Ser Ser Lys Ala 95 100

Asn Leu Ser Gly Gly Val Trp Lys Asp Asn Ile Asn Met Ala Leu 110 115 120 Asn Leu Ser Gly Gly Val Trp Lys Asp Asn Ile Asn Met Ala Leu 110 115 120

Val Val Asp Thr Tyr Tyr Asp Asp Gln Leu Ile Ser Cys Gly Ser 125 130 135 Val Val Asp Thr Tyr Tyr Asp Asp Gln Leu Ile Ser Cys Gly Ser 125 130 135

Val Asn Arg Gly Thr Cys Gln Arg His Val Phe Pro His Asn His 140 145 150 Val Asn Arg Gly Thr Cys Gln Arg His Val Phe Pro His Asn His 140 145 150

Thr Ala Asp Ile Gln Ser Glu Val His Cys Ile Phe Ser Pro Gln 155 160 165 Thr Ala Asp Ile Gln Ser Glu Val His Cys Ile Phe Ser Pro Gln 155 160 165

Ile Glu Glu Pro Ser Gln Cys Pro Asp Cys Val Val Ser Ala Leu 170 175 180 Ile Glu Glu Pro Ser Gln Cys Pro Asp Cys Val Val Ser Ala Leu 170 175 180

Gly Ala Lys Val Leu Ser Ser Val Lys Asp Arg Phe Ile Asn Phe 185 190 195 Gly Ala Lys Val Leu Ser Ser Val Lys Asp Arg Phe Ile Asn Phe 185 190 195

Phe Val Gly Asn Thr Ile Asn Ser Ser Tyr Phe Pro Asp His Pro 200 205 210 Phe Val Gly Asn Thr Ile Asn Ser Ser Tyr Phe Pro Asp His Pro 200 205 210

Leu His Ser Ile Ser Val Arg Arg Leu Lys Glu Thr Lys Asp Gly 215 220 225 Leu His Ser Ile Ser Val Arg Arg Leu Lys Glu Thr Lys Asp Gly 215 220 225

Phe Met Phe Leu Thr Asp Gln Ser Tyr Ile Asp Val Leu Pro Glu 230 235 240 Phe Met Phe Leu Thr Asp Gln Ser Tyr Ile Asp Val Leu Pro Glu 230 235 240

Phe Arg Asp Ser Tyr Pro Ile Lys Tyr Val His Ala Phe Glu Ser 245 250 255 Phe Arg Asp Ser Tyr Pro Ile Lys Tyr Val His Wing Phe Glu Ser 245 250 255

Asn Asn Phe Ile Tyr Phe Leu Thr Val Gln Arg Glu Thr Leu Asp 260 265 270 Asn Asn Phe Ile Tyr Phe Leu Thr Val Gln Arg Glu Thr Leu Asp 260 265 270

Ala Gln Thr Phe His Thr Arg Ile Ile Arg Phe Cys Ser Ile Asn 275 280 285 Gln Wing Thr Phe His Thr Arg Ile Arg Phe Cys Ser Ile Asn 275 280 285

Ser Gly Leu His Ser Tyr Met Glu Met Pro Leu Glu Cys Ile Leu 290 295 300 Ser Gly Leu His Ser Tyr Met Glu Met Pro Leu Glu Cys Ile Leu 290 295 300

Thr Glu Lys Arg Lys Lys Arg Ser Thr Lys Lys Glu Val Phe Asn 305 310 315 Thr Glu Lys Arg Lys Lys Arg Ser Thr Lys Lys Glu Val Phe Asn 305 310 315

Ile Leu Gln Ala Ala Tyr Val Ser Lys Pro Gly Ala Gln Leu Ala 320 325 330 Ile Leu Gln Wing Wing Tyr Val Ser Lys Pro Gly Wing Gln Leu Wing 320 325 330

Arg Gln Ile Gly Ala Ser Leu Asn Asp Asp Ile Leu Phe Gly Val 335 340 345 Arg Gln Ile Gly Ala Ser Leu Asn Asp Asp Ile Leu Phe Gly Val 335 340 345

Phe Ala Gln Ser Lys Pro Asp Ser Ala Glu Pro Met Asp Arg Ser 350 355 360 Phe Ala Gln Ser Lys Pro Asp Ser Ala Glu Pro Met Asp Arg Ser 350 355 360

Ala Met Cys Ala Phe Pro Ile Lys Tyr Val Asn Asp Phe Phe Asn 365 370 375 Wing Met Cys Wing Phe Pro Ile Lys Tyr Val Asn Asp Phe Phe Asn 365 370 375

Lys Ile Val Asn Lys Asn Asn Val Arg Cys Leu Gln His Phe Tyr 380 385 390 Lys Ile Val Asn Lys Asn Asn Val Arg Cys Leu Gln His Phe Tyr 380 385 390

Gly Pro Asn His Glu His Cys Phe Asn Arg Thr Leu Leu Arg Asn 395 400 405 Gly Pro Asn His Glu His Cys Phe Asn Arg Thr Leu Leu Arg Asn 395 400 405

Ser Ser Gly Cys Glu Ala Arg Arg Asp Glu Tyr Arg Thr Glu Phe 410 415 420 Ser Ser Gly Cys Glu Ala Arg Arg Asp Glu Tyr Arg Thr Glu Phe 410 415 420

Thr Thr Ala Leu Gln Arg Val Asp Leu Phe Met Gly Gln Phe Ser Thr Thr Ala Leu Gln Arg Val Asp Leu Phe Met Gly Gln Phe Ser

425 430 425 430

Glu Val Leu Leu Thr Ser Ile Ser Thr Phe Ile Lys Gly Asp Leu 440 445 450 Glu Val Leu Leu Thr Ser Ile Ser Thr Phe Ile Lys Gly Asp Leu 440 445 450

Thr Ile Ala Asn Leu Gly Thr Ser Glu Gly Arg Phe Met Gln Val 455 460 465 Thr Ile Ala Asn Leu Gly Thr Ser Glu Gly Arg Phe Met Gln Val 455 460 465

Val Val Ser Arg Ser Gly Pro Ser Thr Pro His Val Asn Phe Leu 470 475 480 Val Val Ser Arg Ser Gly Pro Ser Thr Pro His Val Asn Phe Leu 470 475 480

Leu Asp Ser His Pro Val Ser Pro Glu Val Ile Val Glu His Thr 485 490 495 Leu Asp Ser His Pro Val Ser Pro Glu Val Ile Val Glu His Thr 485 490 495

Leu Asn Gln Asn Gly Tyr Thr Leu Val Ile Thr Gly Lys Lys Ile 500 505 510 Leu Asn Gln Asn Gly Tyr Thr Leu Val Ile Thr Gly Lys Lys Ile 500 505 510

Thr Lys Ile Pro Leu Asn Gly Leu Gly Cys Arg His Phe Gln Ser 515 520 525 Thr Lys Ile Pro Leu Asn Gly Leu Gly Cys Arg His Phe Gln Ser 515 520 525

Cys Ser Gln Cys Leu Ser Ala Pro Pro Phe Val Gln Cys Gly Trp 530 535 540 Cys Ser Gln Cys Leu Ser Ala Pro Pro Phe Val Gln Cys Gly Trp 530 535 540

Cys His Asp Lys Cys Val Arg Ser Glu Glu Cys Leu Ser Gly Thr 545 550 555 Cys His Asp Lys Cys Val Arg Ser Glu Glu Cys Leu Ser Gly Thr 545 550 555

Trp Thr Gln Gln Ile Cys Leu Pro Ala Ile Tyr Lys Val Phe Pro 560 565 570 Trp Thr Gln Gln Ile Cys Leu Pro Wing Ile Tyr Lys Val Phe Pro 560 565 570

Asn Ser Ala Pro Leu Glu Gly Gly Thr Arg Leu Thr Ile Cys Gly 575 580 585 Asn Ser Ala Pro Leu Glu Gly Gly Thr Arg Leu Thr Ile Cys Gly 575 580 585

Trp Asp Phe Gly Phe Arg Arg Asn Asn Lys Phe Asp Leu Lys Lys 590 595 600 Trp Asp Phe Gly Phe Arg Arg Asn Asn Lys Phe Asp Leu Lys Lys 590 595 600

Thr Arg Val Leu Leu Gly Asn Glu Ser Cys Thr Leu Thr Leu Ser 605 610 615 Thr Arg Val Leu Leu Gly Asn Glu Ser Cys Thr Leu Thr Leu Ser 605 610 615

Glu Ser Thr Met Asn Thr Leu Lys Cys Thr Val Gly Pro Ala Met 620 625 630 Glu Ser Thr Met Asn Thr Leu Lys Cys Thr Val Gly Pro Wing Met 620 625 630

Asn Lys His Phe Asn Met Ser Ile Ile Ile Ser Asn Gly His Gly 635 640 645 Asn Lys His Phe Asn Met Ser Ile Ile Ile Ser Asn Gly His Gly 635 640 645

Thr Thr Gln Tyr Ser Thr Phe Ser Tyr Val Asp Pro Val Ile Thr 650 655 660 Thr Thr Gln Tyr Ser Thr Phe Ser Tyr Val Asp Pro Val Ile Thr 650 655 660

Ser Ile Ser Pro Lys Tyr Gly Pro Met Ala Gly Gly Thr Leu Leu 665 670 675 Be Ile Be Pro Lys Tyr Gly Pro Met Wing Gly Gly Thr Leu Leu 665 670 675

Thr Leu Thr Gly Asn Tyr Leu Asn Ser Gly Asn Ser Arg His Ile 680 685 690 Thr Leu Thr Gly Asn Tyr Leu Asn Ser Gly Asn Ser Arg His Ile 680 685 690

Ser Ile Gly Gly Lys Thr Cys Thr Leu Lys Ser Val Ser Asn Ser 695 700 705 Ser Ile Gly Gly Lys Thr Cys Thr Leu Lys Ser Val Ser Asn Ser 695 700 705

Ile Leu Glu Cys Tyr Thr Pro Ala Gln Thr Ile Ser Thr Glu Phe 710 715 720 Ile Leu Glu Cys Tyr Thr Pro Wing Gln Thr Ile Ser Thr Glu Phe 710 715 720

Ala Val Lys Leu Lys Ile Asp Leu Ala Asn Arg Glu Thr Ser Ile 725 730 735 Wing Val Lys Leu Lys Ile Asp Leu Wing Asn Arg Glu Thr Ser Ile 725 730 735

Phe Ser Tyr Arg Glu Asp Pro Ile Val Tyr Glu Ile His Pro Thr 740 745 750 Phe Ser Tyr Arg Glu Asp Pro Ile Val Tyr Glu Ile His Pro Thr 740 745 750

Lys Ser Phe Ile Ser Thr Trp Trp Lys Glu Pro Leu Asn Ile Val 755 760 Lys Ser Phe Ile Ser Thr Trp Trp Lys Glu Pro Leu Asn Ile Val 755 760

Ser Phe Leu Phe Cys Phe Ala Ser Gly Gly Ser Thr Ile Thr Gly 770 775 Be Phe Leu Phe Cys Phe Ala Be Gly Gly Ser Thr Ile Thr Gly 770 775

Val Gly Lys Asn Leu Asn Ser Val Ser Val Pro Arg Met Val Ile 785 790 795 Val Gly Lys Asn Leu Asn Ser Val Ser Val Pro Arg Met Val Ile 785 790 795

Asn Val His Glu Ala Gly Arg Asn Phe Thr Val Ala Cys Gln His 800 805 810 Asn Val His Glu Ala Gly Arg Asn Phe Thr Val Ala Cys Gln His 800 805 810

Arg Ser Asn Ser Glu Ile Ile Cys Cys Thr Thr Pro Ser Leu Gln 815 820 825 Arg Ser Asn Ser Glu Ile Ile Cys Cys Thr Thr Pro Ser Leu Gln 815 820 825

Gln Leu Asn Leu Gln Leu Pro Leu Lys Thr Lys Ala Phe Phe Met 830 835 840 Gln Leu Asn Leu Gln Leu Pro Leu Lys Thr Lys Wing Phe Phe Met 830 835 840

Leu Asp Gly Ile Leu Ser Lys Tyr Phe Asp Leu Ile Tyr Val His 845 850 855 Leu Asp Gly Ile Leu Ser Lys Tyr Phe Asp Leu Ile Tyr Val His 845 850 855

Asn Pro Val Phe Lys Pro Phe Glu Lys Pro Val Met Ile Ser Met 860 865 870 Asn Pro Val Phe Lys Pro Phe Glu Lys Pro Val Met Ile Ser Met 860 865 870

Gly Asn Glu Asn Val Leu Glu Ile Lys Gly Asn Asp Ile Asp Pro 875 880 885 Gly Asn Glu Asn Val Leu Glu Ile Lys Gly Asn Asp Ile Asp Pro 875 880 885

Glu Ala Val Lys Gly Glu Val Leu Lys Val Gly Asn Lys Ser Cys 890 895 900 Glu Ala Val Lys Gly Glu Val Leu Lys Val Gly Asn Lys Ser Cys 890 895 900

Glu Asn Ile His Leu His Ser Glu Ala Val Leu Cys Thr Val Pro 905 910 915 Glu Asn Ile His Leu His Ser Glu Ala Val Leu Cys Thr Val Pro 905 910 915

Asn Asp Leu Leu Lys Leu Asn Ser Glu Leu Asn Ile Glu Trp Lys 920 925 930 Asn Asp Leu Leu Lys Leu Asn Ser Glu Leu Asn Ile Glu Trp Lys 920 925 930

Gln Ala Ile Ser Ser Thr Val Leu Gly Lys Val Ile Val Gln Pro 935 940 945 Gln Wing Ile Ser Ser Thr Val Leu Gly Lys Val Ile Val Gln Pro 935 940 945

Asp Gln Asn Phe Thr Gly Leu Ile Ala Gly Val Val Ser Ile Ser 950 955 960 Asp Gln Asn Phe Thr Gly Leu Ile Wing Gly Val Val Ser Ile Ser 950 955 960

Thr Ala Leu Leu Leu Leu Leu Gly Phe Phe Leu Trp Leu Lys Lys 965 970 975 Thr Ala Leu Leu Leu Leu Leu Gly Phe Phe Leu Trp Leu Lys Lys 965 970 975

Arg Lys Gln Ile Lys Asp Leu Gly Ser Glu Leu Val Arg Tyr Asp 980 985 990 Arg Lys Gln Ile Lys Asp Leu Gly Ser Glu Leu Val Arg Tyr Asp 980 985 990

Ala Arg Val His Thr Pro His Leu Asp Arg Leu Val Ser Ala Arg 995 1000 1005 Ala Arg Val His Thr Pro His Leu Asp Arg Leu Val Ser Ala Arg 995 1000 1005

Ser Val Ser Pro Thr Thr Glu Met Val Ser Asn Glu Ser Val Asp 1010 1015 1020 Ser Val Ser Pro Thr Thr Glu Met Val Ser Asn Glu Ser Val Asp 1010 1015 1020

Tyr Arg Ala Thr Phe Pro Glu Asp Gln Phe Pro Asn Ser Ser Gln 1025 1030 1035 Tyr Arg Wing Thr Phe Pro Glu Asp Gln Phe Pro Asn Ser Ser Gln 1025 1030 1035

Asn Gly Ser Cys Arg Gln Val Gln Tyr Pro Leu Thr Asp Met Ser 1040 1045 1050 Asn Gly Ser Cys Arg Gln Val Gln Tyr Pro Leu Thr Asp Met Ser 1040 1045 1050

Pro Ile Leu Thr Ser Gly Asp Ser Asp Ile Ser Ser Pro Leu Leu 1055 1060 1065 Pro Ile Leu Thr Be Gly Asp Be Asp Ile Be Be Pro Leu Leu 1055 1060 1065

Gln Asn Thr Val His Ile Asp Leu Ser Ala Leu Asn Pro Glu Leu 1070 1075 1080 Gln Asn Thr Val His Ile Asp Leu Ser Ala Leu Asn Pro Glu Leu 1070 1075 1080

Val Gln Ala Val Gln His Val Val Ile Gly Pro Ser Ser Leu Ile 1085 1090 1095 Val Gln Wing Val Gln His Val Val Ile Gly Pro Ser Ser Leu Ile 1085 1090 1095

Val His Phe Asn Glu Val Ile Gly Arg Gly His Phe Gly Cys Val 1100 1105 1110 Val His Phe Asn Glu Val Ile Gly Arg Gly His Phe Gly Cys Val 1100 1105 1110

Tyr His Gly Thr Leu Leu Asp Asn Asp Gly Lys Lys Ile His Cys 1115 1120 1125 Tyr His Gly Thr Leu Leu Asp Asn Asp Gly Lys Lys Ile His Cys 1115 1120 1125

Ala Val Lys Ser Leu Asn Arg Ile Thr Asp Ile Gly Glu Val Ser 1130 1135 1140 Wing Val Lys Ser Leu Asn Arg Ile Thr Asp Ile Gly Glu Val Ser 1130 1135 1140

Gln Phe Leu Thr Glu Gly Ile Ile Met Lys Asp Phe Ser His Pro 1145 1150 1155 Gln Phe Leu Thr Glu Gly Ile Ile Met Lys Asp Phe Ser His Pro 1145 1150 1155

Asn Val Leu Ser Leu Leu Gly Ile Cys Leu Arg Ser Glu Gly Ser 1160 1165 1170 Asn Val Leu Ser Leu Leu Gly Ile Cys Leu Arg Ser Glu Gly Ser 1160 1165 1170

Pro Leu Val Val Leu Pro Tyr Met Lys His Gly Asp Leu Arg Asn 1175 1180 1185 Pro Leu Val Val Leu Pro Tyr Met Lys His Gly Asp Leu Arg Asn 1175 1180 1185

Phe Ile Arg Asn Glu Thr His Asn Pro Thr Val Lys Asp Leu Ile 1190 1195 1200 Phe Ile Arg Asn Glu Thr His Asn Pro Thr Val Lys Asp Leu Ile 1190 1195 1200

Gly Phe Gly Leu Gln Val Ala Lys Gly Met Lys Tyr Leu Ala Ser 1205 1210 1215 Gly Phe Gly Leu Gln Val Wing Lys Gly Met Lys Tyr Leu Wing Ser 1205 1210 1215

Lys Lys Phe Val His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu 1220 1225 1230 Lys Lys Phe Val His Arg Asp Leu Ala Wing Arg Asn Cys Met Leu 1220 1225 1230

Asp Glu Lys Phe Thr Val Lys Val Ala Asp Phe Gly Leu Ala Arg 1235 1240 1245 Asp Glu Lys Phe Thr Val Lys Val Wing Asp Phe Gly Leu Wing Arg 1235 1240 1245

Asp Met Tyr Asp Lys Glu Tyr Tyr Ser Val His Asn Lys Thr Gly 1250 1255 1260 Asp Met Tyr Asp Lys Glu Tyr Tyr Ser Val His Asn Lys Thr Gly 1250 1255 1260

Ala Lys Leu Pro Val Lys Trp Met Ala Leu Glu Ser Leu Gln Thr 1265 1270 1275 Wing Lys Leu Pro Val Lys Trp Met Wing Leu Glu Ser Leu Gln Thr 1265 1270 1275

Gln Lys Phe Thr Thr Lys Ser Asp Val Trp Ser Phe Gly Val Leu 1280 1285 1290 Gln Lys Phe Thr Thr Lys Ser Asp Val Trp Ser Phe Gly Val Leu 1280 1285 1290

Leu Trp Glu Leu Met Thr Arg Gly Ala Pro Pro Tyr Pro Asp Val 1295 1300 1305 Leu Trp Glu Leu Met Thr Arg Gly Ala Pro Pro Tyr Pro Asp Val 1295 1300 1305

Asn Thr Phe Asp Ile Thr Val Tyr Leu Leu Gln Gly Arg Arg Leu 1310 1315 1320 Asn Thr Phe Asp Ile Thr Val Tyr Leu Leu Gln Gly Arg Arg Leu 1310 1315 1320

Leu Gln Pro Glu Tyr Cys Pro Asp Pro Leu Tyr Glu Val Met Leu 1325 1330 1335 Leu Gln Pro Glu Tyr Cys Pro Asp Pro Leu Tyr Glu Val Met Leu 1325 1330 1335

Lys Cys Trp His Pro Lys Ala Glu Met Arg Pro Ser Phe Ser Glu 1340 1345 1350 Lys Cys Trp His Pro Lys Ala Glu Met Arg Pro Ser Phe Ser Glu 1340 1345 1350

Leu Val Ser Arg Ile Ser Ala Ile Phe Ser Thr Phe Ile Gly Glu 1355 1360 1365 Leu Val Ser Arg Ile Ser Ala Ile Phe Ser Thr Phe Ile Gly Glu 1355 1360 1365

His Tyr Val His Val Asn Ala Thr Tyr Val Asn Val Lys Cys Val 1370 1375 1380 His Tyr Val His Val Asn Ala Thr Tyr Val Asn Val Lys Cys Val 1370 1375 1380

Ala Pro Tyr Pro Ser Leu Leu Ser Ser Glu Asp Asn Ala Asp Asp 1385 1390 1395 Ala Pro Tyr Pro Ser Leu Leu Ser Ser Glu Asp Asn Ala Asp Asp 1385 1390 1395

Glu Val Asp Thr Arg Pro Ala Ser Phe Trp Glu Thr Ser 1400 1405 Glu Val Asp Thr Arg Pro Ala Ser Phe Trp Glu Thr Ser 1400 1405

<210> 48 <210> 48

<211> 512 <211> 512

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 48<400> 48

Met Ala His Ser Cys Arg Trp Arg Phe Pro Ala Arg Pro Gly Thr Met Ala His Ser Cys Arg Trp Arg Phe Pro Ala Arg Pro Gly Thr

1 5 10 15 1 5 10 15

Thr Gly Gly Gly Gly Gly Gly Gly Arg Arg Gly Leu Gly Gly Ala 20 25 30 Thr Gly Gly Gly Gly Gly Gly Gly Arg Arg Gly Leu Gly Gly Wing 20 25 30

Pro Arg Gln Arg Val Pro Ala Leu Leu Leu Pro Pro Gly Pro Pro 35 40 45 Pro Arg Gln Arg Val Pro Ala Leu Leu Leu Pro Pro Gly Pro Pro 35 40 45

Val Gly Gly Gly Gly Pro Gly Ala Pro Pro Ser Pro Pro Ala Val 50 55 60 Val Gly Gly Gly Gly Pro Gly Ala Pro Pro Ser Pro Pro Ala Val 50 55 60

Ala Ala Ala Ala Ala Ala Ala Gly Ser Ser Gly Ala Gly Val Pro 65 70 75 Wing Wing Wing Wing Wing Wing Gly Ser Ser Gly Wing Gly Val Pro 65 70 75

Gly Gly Ala Ala Ala Ala Ser Ala Ala Ser Ser Ser Ser Ala Ser 80 85 90 Gly Gly Wing Wing Wing Be Wing Wing Be Be Be Be Wing Be 80 85 90

Ser Ser Ser Ser Ser Ser Ser Ser Ala Ser Ser Gly Pro Ala Leu 95 100 105 Be Be Be Be Be Be Be Be Be Be Be Gly Pro Wing Leu 95 100 105

Leu Arg Val Gly Pro Gly Phe Asp Ala Ala Leu Gln Val Ser Ala 110 115 120 Leu Arg Val Gly Pro Gly Phe Asp Wing Wing Leu Gln Val Ser Wing 110 115 120

Ala Ile Gly Thr Asn Leu Arg Arg Phe Arg Ala Val Phe Gly Glu 125 130 135 Wing Ile Gly Thr Asn Leu Arg Arg Phe Arg Wing Val Phe Gly Glu 125 130 135

Ser Gly Gly Gly Gly Gly Ser Gly Glu Leu Thr Thr Gln Ile Pro 140 145 150 Ser Gly Gly Gly Gly Gly Ser Gly Glu Leu Thr Thr Gln Ile Pro 140 145 150

Cys Ser Trp Arg Thr Lys Gly His Ile His Asp Lys Lys Thr Glu 155 160 165 Cys Ser Trp Arg Thr Lys Gly His Ile His Asp Lys Lys Thr Glu 155 160 165

Pro Phe Arg Leu Leu Ala Trp Ser Trp Cys Leu Asn Asp Glu Gln 170 175 180 Pro Phe Arg Leu Leu Wing Trp Ser Trp Cys Leu Asn Asp Glu Gln 170 175 180

Phe Leu Gly Phe Gly Ser Asp Glu Glu Val Arg Val Arg Ser Pro 185 190 195 Phe Leu Gly Phe Gly Ser Asp Glu Glu Val Arg Val Arg Ser Pro 185 190 195

Thr Arg Ser Pro Ser Val Lys Thr Ser Pro Arg Lys Pro Arg Gly 200 205 210 Thr Arg Ser Pro Ser Val Lys Thr Ser Pro Arg Lys Pro Arg Gly 200 205 210

Arg Pro Arg Ser Gly Ser Asp Arg Asn Ser Ala Ile Leu Ser Asp 215 220 225 Arg Pro Arg Ser Gly Ser Asp Arg Asn Ser Ala Ile Leu Ser Asp 215 220 225

Pro Ser Val Phe Ser Pro Leu Asn Lys Ser Glu Thr Lys Ser Gly 230 235 240 Pro Ser Val Phe Ser Pro Leu Asn Lys Ser Glu Thr Lys Ser Gly 230 235 240

Asp Lys Ile Lys Lys Lys Asp Ser Lys Ser Ile Glu Lys Lys Arg 245 250 255 Asp Lys Ile Lys Lys Lys Asp Ser Lys Ser Ile Glu Lys Lys Arg 245 250 255

Gly Arg Pro Pro Thr Phe Pro Gly Val Lys Ile Lys Ile Thr His 260 265 270 Gly Arg Pro Pro Thr Phe Pro Gly Val Lys Ile Lys Ile Thr His 260 265 270

Gly Lys Asp Ile Ser Glu Leu Pro Lys Gly Asn Lys Glu Asp Ser 275 280 285 Gly Lys Asp Ile Ser Glu Leu Pro Lys Gly Asn Lys Glu Asp Ser 275 280 285

Leu Lys Lys Ile Lys Arg Thr Pro Ser Ala Thr Phe Gln Gln Ala 290 295 300 Leu Lys Lys Ile Lys Arg Thr Pro Ser Wing Thr Phe Gln Gln Wing 290 295 300

Thr Lys Ile Lys Lys Leu Arg Ala Gly Lys Leu Ser Pro Leu Lys 305 310 315 Thr Lys Ile Lys Lys Leu Arg Wing Gly Lys Leu Ser Pro Leu Lys 305 310 315

Ser Lys Phe Lys Thr Gly Lys Leu Gln Ile Gly Arg Lys Gly Val 320 325 330 Ser Lys Phe Lys Thr Gly Lys Leu Gln Ile Gly Arg Lys Gly Val 320 325 330

Gln Ile Val Arg Arg Arg Gly Arg Pro Pro Ser Thr Glu Arg Ile 335 340 Gln Ile Val Arg Arg Arg Gly Arg Pro Pro Ser Thr Glu Arg Ile 335 340

Lys Thr Pro Ser Gly Leu Leu Ile Asn Ser Glu Leu Glu Lys Pro 350 355 360 Lys Thr Pro Ser Gly Leu Leu Ile Asn Ser Glu Leu Glu Lys Pro 350 355 360

Gln Lys Val Arg Lys Asp Lys Glu Gly Thr Pro Pro Leu Thr Lys 365 370 375 Gln Lys Val Arg Lys Asp Lys Glu Gly Thr Pro Pro Leu Thr Lys 365 370 375

Glu Asp Lys Thr Val Val Arg Gln Ser Pro Arg Arg Ile Lys Pro 380 385 390 Glu Asp Lys Thr Val Val Arg Gln Ser Pro Arg Arg Ile Lys Pro 380 385 390

Val Arg Ile Ile Pro Ser Ser Lys Arg Thr Asp Ala Thr Ile Ala 395 400 405 Val Arg Ile Ile Pro Ser Ser Lys Arg Thr Asp Ala Thr Ile Ala 395 400 405

Lys Gln Leu Leu Gln Arg Ala Lys Lys Gly Ala Gln Lys Lys Ile 410 415 420 Lys Gln Leu Leu Gln Arg Wing Lys Lys Gly Wing Gln Lys Lys Ile 410 415 420

Glu Lys Glu Ala Ala Gln Leu Gln Gly Arg Lys Val Lys Thr Gln 425 430 435 Glu Lys Glu Wing Gln Leu Gln Gly Arg Lys Val Lys Thr Gln 425 430 435

Val Lys Asn Ile Arg Gln Phe Ile Met Pro Val Val Ser Ala Ile 440 445 450 Val Lys Asn Ile Arg Gln Phe Ile Met Pro Val Val Ser Wing Ile 440 445 450

Ser Ser Arg Ile Ile Lys Thr Pro Arg Arg Phe Ile Glu Asp Glu 455 460 465 Ser Ser Arg Ile Ile Lys Thr Pro Arg Arg Phe Ile Glu Asp Glu 455 460 465

Asp Tyr Asp Pro Pro Ile Lys Ile Ala Arg Leu Glu Ser Thr Pro 470 475 480 Asp Tyr Asp Pro Pro Ile Lys Ile Ala Arg Leu Glu Ser Thr Pro 470 475 480

Asn Ser Arg Phe Ser Ala Pro Ser Cys Gly Ser Ser Glu Lys Ser 485 490 495 Asn Ser Arg Phe Ser Ala Pro Ser Cys Gly Ser Ser Glu Lys Ser 485 490 495

Ser Ala Ala Ser Gln His Ser Ser Gln Met Ser Ser Asp Ser Ser 500 505 510 Be Wing Be Be Gln His Be Be Gln Met Be Be Asp Be Be 500 505 510

Arg Ser Arg Ser

<210> 49 <210> 49

<211> 2839 <211> 2839

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 49 Met Ala Ala His Arg Pro Val Glu Trp Val Gln Ala Val Val Ser 1 5 10 15 <400> 49 Met Ala Wing His Arg Pro Val Glu Trp Val Gln Ala Val Val Ser 1 5 10 15

Arg Phe Asp Glu Gln Leu Pro Ile Lys Thr Gly Gln Gln Asn Thr 20 25 30 Arg Phe Asp Glu Gln Leu Pro Ile Lys Thr Gly Gln Gln Asn Thr 20 25 30

His Thr Lys Val Ser Thr Glu His Asn Lys Glu Cys Leu Ile Asn 35 40 45 His Thr Lys Val Ser Thr Glu His Asn Lys Glu Cys Leu Ile Asn 35 40 45

Ile Ser Lys Tyr Lys Phe Ser Leu Val Ile Ser Gly Leu Thr Thr 50 55 60 Ile Ser Lys Tyr Lys Phe Ser Leu Val Ile Ser Gly Leu Thr Thr 50 55 60

Ile Leu Lys Asn Val Asn Asn Met Arg Ile Phe Gly Glu Ala Ala 65 70 75 Ile Leu Lys Asn Val Asn Asn Met Arg Ile Phe Gly Glu Wing Wing 65 70 75

Glu Lys Asn Leu Tyr Leu Ser Gln Leu Ile Ile Leu Asp Thr Leu 80 85 90 Glu Lys Asn Leu Tyr Leu Ser Gln Leu Ile Ile Leu Asp Thr Leu 80 85 90

Glu Lys Cys Leu Ala Gly Gln Pro Lys Asp Thr Met Arg Leu Asp 95 100 105 Glu Lys Cys Leu Wing Gly Gln Pro Lys Asp Thr Met Arg Leu Asp 95 100 105

Glu Thr Met Leu Val Lys Gln Leu Leu Pro Glu Ile Cys His Phe 110 115 120 Glu Thr Met Leu Val Lys Gln Leu Leu Pro Glu Ile Cys His Phe 110 115 120

Leu His Thr Cys Arg Glu Gly Asn Gln His Ala Ala Glu Leu Arg 125 130 135 Asn Ser Ala Ser Gly Val Leu Phe Ser Leu Ser Cys Asn Asn Phe 140 145 Leu His Thr Cys Arg Glu Gly Asn Gln His Wing Glu Glu Leu Arg 125 130 135 Asn Be Wing Be Gly Val Leu Phe Be Leu Be Cys Asn Asn Phe 140 145

Asn Ala Val Phe Ser Arg Ile Ser Thr Arg Leu Gln Glu Leu Thr 155 160 165 Asn Ala Val Phe Ser Arg Ile Ser Thr Arg Leu Gln Glu Leu Thr 155 160 165

Val Cys Ser Glu Asp Asn Val Asp Val His Asp Ile Glu Leu Leu 170 175 180 Val Cys Ser Glu Asp Asn Val Asp Val His Asp Ile Glu Leu Leu 170 175 180

Gln Tyr Ile Asn Val Asp Cys Ala Lys Leu Lys Arg Leu Leu Lys 185 190 195 Gln Tyr Ile Asn Val Asp Cys Ala Lys Leu Lys Arg Leu Leu Lys 185 190 195

Glu Thr Ala Phe Lys Phe Lys Ala Leu Lys Lys Val Ala Gln Leu 200 205 210 Glu Thr Wing Phe Lys Phe Lys Wing Leu Lys Lys Val Wing Gln Leu 200 205 210

Ala Val Ile Asn Ser Leu Glu Lys Ala Phe Trp Asn Trp Val Glu 215 220 225 Wing Val Ile Asn Ser Leu Glu Lys Wing Phe Trp Asn Trp Val Glu 215 220 225

Asn Tyr Pro Asp Glu Phe Thr Lys Leu Tyr Gln Ile Pro Gln Thr 230 235 240 Asn Tyr Pro Asp Glu Phe Thr Lys Leu Tyr Gln Ile Pro Gln Thr 230 235 240

Asp Met Ala Glu Cys Ala Glu Lys Leu Phe Asp Leu Val Asp Gly 245 250 255 Asp Met Glu Cys Wing Glu Lys Wing Leu Phe Asp Leu Val Asp Gly 245 250 255

Phe Ala Glu Ser Thr Lys Arg Lys Ala Ala Val Trp Pro Leu Gln 260 265 270 Phe Wing Glu Ser Thr Lys Arg Lys Wing Wing Val Trp Pro Leu Gln 260 265 270

Ile Ile Leu Leu Ile Leu Cys Pro Glu Ile Ile Gln Asp Ile Ser 275 280 285 Ile Ile Leu Leu Ile Leu Cys Pro Glu Ile Ile Gln Asp Ile Ser 275 280 285

Lys Asp Val Val Asp Glu Asn Asn Met Asn Lys Lys Leu Phe Leu 290 295 300 Lys Asp Val Val Asp Glu Asn Asn Met Asn Lys Lys Leu Phe Leu 290 295 300

Asp Ser Leu Arg Lys Ala Leu Ala Gly His Gly Gly Ser Arg Gln 305 310 315 Asp Ser Leu Arg Lys Ala Leu Ala Gly His Gly Gly Ser Arg Gln 305 310 315

Leu Thr Glu Ser Ala Ala Ile Ala Cys Val Lys Leu Cys Lys Ala 320 325 330 Leu Thr Glu Ser Wing Ile Wing Cys Val Lys Leu Cys Lys Wing 320 325 330

Ser Thr Tyr Ile Asn Trp Glu Asp Asn Ser Val Ile Phe Leu Leu 335 340 345 Ser Thr Tyr Ile Asn Trp Glu Asp Asn Ser Val Ile Phe Leu Leu 335 340 345

Val Gln Ser Met Val Val Asp Leu Lys Asn Leu Leu Phe Asn Pro 350 355 360 Val Gln Ser Met Val Val Asp Leu Lys Asn Leu Leu Phe Asn Pro 350 355 360

Ser Lys Pro Phe Ser Arg Gly Ser Gln Pro Ala Asp Val Asp Leu 365 370 375 Ser Lys Pro Phe Ser Arg Gly Ser Gln Pro Ala Asp Val Asp Leu 365 370 375

Met Ile Asp Cys Leu Val Ser Cys Phe Arg Ile Ser Pro His Asn 380 385 390 Met Ile Asp Cys Leu Val Ser Cys Phe Arg Ile Ser Pro His Asn 380 385 390

Asn Gln His Phe Lys Ile Cys Leu Ala Gln Asn Ser Pro Ser Thr 395 400 405 Asn Gln His Phe Lys Ile Cys Leu Wing Gln Asn Ser Pro Ser Thr 395 400 405

Phe His Tyr Val Leu Val Asn Ser Leu His Arg Ile Ile Thr Asn 410 415 420 Phe His Tyr Val Leu Val Asn Ser Leu His Arg Ile Ile Thr Asn 410 415 420

Ser Ala Leu Asp Trp Trp Pro Lys Ile Asp Ala Val Tyr Cys His 425 430 435 Ser Ala Leu Asp Trp Trp Pro Lys Ile Asp Ala Val Tyr Cys His 425 430 435

Ser Val Glu Leu Arg Asn Met Phe Gly Glu Thr Leu His Lys Ala 440 445 450 Ser Val Glu Leu Arg Asn Met Phe Gly Glu Thr Leu His Lys Ala 440 445 450

Val Gln Gly Cys Gly Ala His Pro Ala Ile Arg Met Ala Pro Ser 455 460 465 Val Gln Gly Cys Gly Ala His Pro Ala Ile Arg Met Ala Pro Ser 455 460 465

Leu Thr Phe Lys Glu Lys Val Thr Ser Leu Lys Phe Lys Glu Lys Leu Thr Phe Lys Glu Lys Val Thr Ser Leu Lys Phe Lys Glu Lys

470 475 470 475

Pro Thr Asp Leu Glu Thr Arg Ser Tyr Lys Tyr Leu Leu Leu Ser 485 490 495 Pro Thr Asp Leu Glu Thr Arg Ser Tyr Lys Tyr Leu Leu Leu Ser 485 490 495

Met Val Lys Leu Ile His Ala Asp Pro Lys Leu Leu Leu Cys Asn 500 505 510 Met Val Lys Leu Ile His Wing Asp Pro Lys Leu Leu Leu Cys Asn 500 505 510

Pro Arg Lys Gln Gly Pro Glu Thr Gln Gly Ser Thr Ala Glu Leu 515 520 525 Pro Arg Lys Gln Gly Pro Glu Thr Gln Gly Ser Thr Ala Glu Leu 515 520 525

Ile Thr Gly Leu Val Gln Leu Val Pro Gln Ser His Met Pro Glu 530 535 540 Ile Thr Gly Leu Val Gln Leu Val Pro Gln Ser His Met Pro Glu 530 535 540

Ile Ala Gln Glu Ala Met Glu Ala Leu Leu Val Leu His Gln Leu 545 550 555 Ile Gln Glu Wing Met Glu Wing Leu Leu Val Leu His Gln Leu 545 550 555

Asp Ser Ile Asp Leu Trp Asn Pro Asp Ala Pro Val Glu Thr Phe 560 565 570 Asp Ser Ile Asp Leu Trp Asn Pro Asp Ala Pro Val Glu Thr Phe 560 565 570

Trp Glu Ile Ser Ser Gln Met Leu Phe Tyr Ile Cys Lys Lys Leu 575 580 585 Trp Glu Ile Ser Ser Gln Met Leu Phe Tyr Ile Cys Lys Lys Leu 575 580 585

Thr Ser His Gln Met Leu Ser Ser Thr Glu Ile Leu Lys Trp Leu 590 595 600 Thr Ser His Gln Met Leu Ser Ser Thr Glu Ile Leu Lys Trp Leu 590 595 600

Arg Glu Ile Leu Ile Cys Arg Asn Lys Phe Leu Leu Lys Asn Lys 605 610 615 Arg Glu Ile Leu Ile Cys Arg Asn Lys Phe Leu Leu Lys Asn Lys 605 610 615

Gln Ala Asp Arg Ser Ser Cys His Phe Leu Leu Phe Tyr Gly Val 620 625 630 Gln Ala Asp Arg Ser Ser Cys His Phe Leu Leu Phe Tyr Gly Val 620 625 630

Gly Cys Asp Ile Pro Ser Ser Gly Asn Thr Ser Gln Met Ser Met 635 640 645 Gly Cys Asp Ile Pro Ser Ser Gly Asn Thr Ser Gln Met Ser Met 635 640 645

Asp His Glu Glu Leu Leu Arg Thr Pro Gly Ala Ser Leu Arg Lys 650 655 660 Asp His Glu Glu Leu Leu Arg Thr Pro Gly Ala Ser Leu Arg Lys 650 655 660

Gly Lys Gly Asn Ser Ser Met Asp Ser Ala Ala Gly Cys Ser Gly 665 670 675 Gly Lys Gly Asn Ser Be Met Asp Ser Wing Wing Gly Cys Ser Gly 665 670 675

Thr Pro Pro Ile Cys Arg Gln Ala Gln Thr Lys Leu Glu Val Ala 680 685 690 Thr Pro Pro Ile Cys Arg Gln Wing Gln Thr Lys Leu Glu Val Wing 680 685 690

Leu Tyr Met Phe Leu Trp Asn Pro Asp Thr Glu Ala Val Leu Val 695 700 705 Leu Tyr Met Phe Leu Trp Asn Pro Asp Thr Glu Ala Val Leu Val 695 700 705

Ala Met Ser Cys Phe Arg His Leu Cys Glu Glu Ala Asp Ile Arg 710 715 720 Wing Met Ser Cys Phe Arg His Leu Cys Glu Glu Wing Asp Ile Arg 710 715 720

Cys Gly Val Asp Glu Val Ser Val His Asn Leu Leu Pro Asn Tyr 725 730 735 Cys Gly Val Asp Glu Val Ser Val His Asn Leu Leu Pro Asn Tyr 725 730 735

Asn Thr Phe Met Glu Phe Ala Ser Val Ser Asn Met Met Ser Thr 740 745 750 Asn Thr Phe Met Glu Phe Ala Ser Val Ser Asn Met Met Ser Thr 740 745 750

Gly Arg Ala Ala Leu Gln Lys Arg Val Met Ala Leu Leu Arg Arg 755 760 765 Gly Arg Wing Wing Leu Gln Lys Arg Val Met Wing Leu Leu Arg Arg 755 760 765

Ile Glu His Pro Thr Ala Gly Asn Thr Glu Ala Trp Glu Asp Thr 770 775 780 Ile Glu His Pro Thr Wing Gly Asn Thr Glu Wing Trp Glu Asp Thr 770 775 780

His Ala Lys Trp Glu Gln Ala Thr Lys Leu Ile Leu Asn Tyr Pro 785 790 795 His Wing Lys Trp Glu Gln Wing Thr Lys Leu Ile Leu Asn Tyr Pro 785 790 795

Lys Ala Lys Met Glu Asp Gly Gln Ala Ala Glu Ser Leu His Lys 800 805 Lys Ala Lys Met Glu Asp Gly Gln Ala Ala Glu Ser Leu His Lys 800 805

Thr Ile Val Lys Arg Arg Met Ser His Val Ser Gly Gly Gly Ser 815 820 Thr Ile Val Lys Arg Arg Met Ser His Val Ser Gly Gly Gly Ser 815 820

Ile Asp Leu Ser Asp Thr Asp Ser Leu Gln Glu Trp Ile Asn Met 830 835 840 Ile Asp Leu Ser Asp Thr Asp Ser Leu Gln Glu Trp Ile Asn Met 830 835 840

Thr Gly Phe Leu Cys Ala Leu Gly Gly Val Cys Leu Gln Gln Arg 845 850 855 Thr Gly Phe Leu Cys Ala Leu Gly Gly Val Cys Leu Gln Gln Arg 845 850 855

Ser Asn Ser Gly Leu Ala Thr Tyr Ser Pro Pro Met Gly Pro Val 860 865 870 Ser Asn Ser Gly Leu Ala Thr Tyr Ser Pro Pro Met Gly Pro Val 860 865 870

Ser Glu Arg Lys Gly Ser Met Ile Ser Val Met Ser Ser Glu Gly 875 880 885 Ser Glu Arg Lys Gly Ser Met Ile Ser Val Met Ser Ser Glu Gly 875 880 885

Asn Ala Asp Thr Pro Val Ser Lys Phe Met Asp Arg Leu Leu Ser 890 895 900 Asn Wing Asp Thr Pro Val Ser Lys Phe Met Asp Arg Leu Leu Ser 890 895 900

Leu Met Val Cys Asn His Glu Lys Val Gly Leu Gln Ile Arg Thr 905 910 915 Leu Met Val Cys Asn His Glu Lys Val Gly Leu Gln Ile Arg Thr 905 910 915

Asn Val Lys Asp Leu Val Gly Leu Glu Leu Ser Pro Ala Leu Tyr 920 925 930 Asn Val Lys Asp Leu Val Gly Leu Glu Leu Ser Pro Ala Leu Tyr 920 925 930

Pro Met Leu Phe Asn Lys Leu Lys Asn Thr Ile Ser Lys Phe Phe 935 940 945 Pro Met Leu Phe Asn Lys Leu Lys Asn Thr Ile Ser Lys Phe Phe 935 940 945

Asp Ser Gln Gly Gln Val Leu Leu Thr Asp Thr Asn Thr Gln Phe 950 955 960 Asp Ser Gln Gly Gln Val Leu Leu Thr Asp Thr Asn Thr Gln Phe 950 955 960

Val Glu Gln Thr Ile Ala Ile Met Lys Asn Leu Leu Asp Asn His 965 970 975 Val Glu Gln Thr Ile Ile Wing Met Lys Asn Leu Leu Asp Asn His 965 970 975

Thr Glu Gly Ser Ser Glu His Leu Gly Gln Ala Ser Ile Glu Thr 980 985 990 Thr Glu Gly Ser Ser Glu His Leu Gly Gln Ala Ser Ile Glu Thr 980 985 990

Met Met Leu Asn Leu Val Arg Tyr Val Arg Val Leu Gly Asn Met 995 1000 1005 Met Met Leu Asn Leu Val Arg Tyr Val Arg Val Leu Gly Asn Met 995 1000 1005

Val His Ala Ile Gln Ile Lys Thr Lys Leu Cys Gln Leu Val Glu 1010 1015 1020 Val His Wing Ile Gln Ile Lys Thr Lys Leu Cys Gln Leu Val Glu 1010 1015 1020

Val Met Met Ala Arg Arg Asp Asp Leu Ser Phe Cys Gln Glu Met 1025 1030 1035 Val Met Met Wing Arg Arg Asp Asp Leu Ser Phe Cys Gln Glu Met 1025 1030 1035

Lys Phe Arg Asn Lys Met Val Glu Tyr Leu Thr Asp Trp Val Met 1040 1045 1050 Lys Phe Arg Asn Lys Met Val Glu Tyr Leu Thr Asp Trp Val Met 1040 1045 1050

Gly Thr Ser Asn Gln Ala Ala Asp Asp Asp Val Lys Cys Leu Thr 1055 1060 1065 Gly Thr Ser Asn Gln Wing Asp Asp Asp Asp Val Lys Cys Leu Thr 1055 1060 1065

Arg Asp Leu Asp Gln Ala Ser Met Glu Ala Val Val Ser Leu Leu 1070 1075 1080 Arg Asp Leu Asp Gln Ala Ser Met Glu Ala Val Val Ser Leu Leu 1070 1075 1080

Ala Gly Leu Pro Leu Gln Pro Glu Glu Gly Asp Gly Val Glu Leu 1085 1090 1095 Wing Gly Leu Pro Leu Gln Pro Glu Glu Gly Asp Gly Val Glu Leu 1085 1090 1095

Met Glu Ala Lys Ser Gln Leu Phe Leu Lys Tyr Phe Thr Leu Phe 1100 1105 1110 Met Glu Ala Lys Ser Gln Leu Phe Leu Lys Tyr Phe Thr Leu Phe 1100 1105 1110

Met Asn Leu Leu Asn Asp Cys Ser Glu Val Glu Asp Glu Ser Ala 1115 1120 1125 Met Asn Leu Leu Asn Asp Cys Ser Glu Val Glu Asp Glu Ser Ala 1115 1120 1125

Gln Thr Gly Gly Arg Lys Arg Gly Met Ser Arg Arg Leu Ala Ser 1130 1135 1140 Gln Thr Gly Gly Arg Lys Arg Gly Met Ser Arg Arg Leu Ala Ser 1130 1135 1140

Leu Arg His Cys Thr Val Leu Ala Met Ser Asn Leu Leu Asn Ala 1145 1150 1155 Asn Val Asp Ser Gly Leu Met His Ser Ile Gly Leu Gly Tyr His 1160 1165 1170 Leu Arg His Cys Thr Val Leu Ala Met Ser Asn Leu Leu Asn Ala 1145 1150 1155 Asn Val Asp Ser Gly Leu Met His Ser Ile Gly Leu Gly Tyr His 1160 1165 1170

Lys Asp Leu Gln Thr Arg Ala Thr Phe Met Glu Val Leu Thr Lys 1175 1180 1185 Lys Asp Leu Gln Thr Arg Wing Thr Phe Met Glu Val Leu Thr Lys 1175 1180 1185

Ile Leu Gln Gln Gly Thr Glu Phe Asp Thr Leu Ala Glu Thr Val 1190 1195 1200 Ile Leu Gln Gln Gly Thr Glu Phe Asp Thr Leu Ala Glu Thr Val 1190 1195 1200

Leu Ala Asp Arg Phe Glu Arg Leu Val Glu Leu Val Thr Met Met 1205 1210 1215 Leu Wing Asp Arg Phe Glu Arg Leu Val Glu Leu Val Thr Met Met 1205 1210 1215

Gly Asp Gln Gly Glu Leu Pro Ile Ala Met Ala Leu Ala Asn Val 1220 1225 1230 Gly Asp Gln Gly Glu Leu Pro Ile Wing Met Wing Leu Wing Asn Val 1220 1225 1230

Val Pro Cys Ser Gln Trp Asp Glu Leu Ala Arg Val Leu Val Thr 1235 1240 1245 Val Pro Cys Ser Gln Trp Asp Glu Leu Wing Arg Val Leu Val Thr 1235 1240 1245

Leu Phe Asp Ser Arg His Leu Leu Tyr Gln Leu Leu Trp Asn Met 1250 1255 1260 Leu Phe Asp Ser Arg His Leu Leu Tyr Gln Leu Leu Trp Asn Met 1250 1255 1260

Phe Ser Lys Glu Val Glu Leu Ala Asp Ser Met Gln Thr Leu Phe 1265 1270 1275 Phe Ser Lys Glu Val Glu Leu Wing Asp Ser Met Gln Thr Leu Phe 1265 1270 1275

Arg Gly Asn Ser Leu Ala Ser Lys Ile Met Thr Phe Cys Phe Lys 1280 1285 1290 Arg Gly Asn Ser Leu Ala Ser Lys Ile Met Thr Phe Cys Phe Lys 1280 1285 1290

Val Tyr Gly Ala Thr Tyr Leu Gln Lys Leu Leu Asp Pro Leu Leu 1295 1300 1305 Val Tyr Gly Ala Thr Tyr Leu Gln Lys Leu Leu Asp Pro Leu Leu 1295 1300 1305

Arg Ile Val Ile Thr Ser Ser Asp Trp Gln His Val Ser Phe Glu 1310 1315 1320 Arg Ile Val Ile Thr Ser Ser Asp Trp Gln His Val Ser Phe Glu 1310 1315 1320

Val Asp Pro Thr Arg Leu Glu Pro Ser Glu Ser Leu Glu Glu Asn 1325 1330 1335 Val Asp Pro Thr Arg Leu Glu Pro Ser Glu Ser Leu Glu Glu Asn 1325 1330 1335

Gln Arg Asn Leu Leu Gln Met Thr Glu Lys Phe Phe His Ala Ile 1340 1345 1350 Gln Arg Asn Leu Leu Gln Met Thr Glu Lys Phe Phe His Ala Ile 1340 1345 1350

Ile Ser Ser Ser Ser Glu Phe Pro Pro Gln Leu Arg Ser Val Cys 1355 1360 1365 Ile Be Be Be Be Glu Phe Pro Pro Gln Leu Arg Ser Val Cys 1355 1360 1365

His Cys Leu Tyr Gln Ala Thr Cys His Ser Leu Leu Asn Lys Ala 1370 1375 1380 His Cys Leu Tyr Gln Ala Thr Cys His Ser Leu Leu Asn Lys Ala 1370 1375 1380

Thr Val Lys Glu Lys Lys Glu Asn Lys Lys Ser Val Val Ser Gln 1385 1390 1395 Thr Val Lys Glu Lys Lys Glu Asn Lys Lys Ser Val Val Ser Gln 1385 1390 1395

Arg Phe Pro Gln Asn Ser Ile Gly Ala Val Gly Ser Ala Met Phe 1400 1405 1410 Arg Phe Pro Gln Asn Ser Ile Gly Ala Val Gly Ser Ala Met Phe 1400 1405 1410

Leu Arg Phe Ile Asn Pro Ala Ile Val Ser Pro Tyr Glu Ala Gly 1415 1420 1425 Leu Arg Phe Ile Asn Pro Wing Ile Val Ser Pro Tyr Glu Wing Gly 1415 1420 1425

Ile Leu Asp Lys Lys Pro Pro Pro Arg Ile Glu Arg Gly Leu Lys 1430 1435 1440 Ile Leu Asp Lys Lys Pro Pro Pro Arg Ile Glu Arg Gly Leu Lys 1430 1435 1440

Leu Met Ser Lys Ile Leu Gln Ser Ile Ala Asn His Val Leu Phe 1445 1450 1455 Leu Met Ser Lys Ile Leu Gln Ser Ile Ala Asn His Val Leu Phe 1445 1450 1455

Thr Lys Glu Glu His Met Arg Pro Phe Asn Asp Phe Val Lys Ser 1460 1465 1470 Thr Lys Glu Glu His Met Arg Pro Phe Asn Asp Phe Val Lys Ser 1460 1465 1470

Asn Phe Asp Ala Ala Arg Arg Phe Phe Leu Asp Ile Ala Ser Asp 1475 1480 1485 Asn Phe Asp Wing Wing Arg Arg Phe Phe Leu Asp Ile Wing Being Asp 1475 1480 1485

Cys Pro Thr Ser Asp Ala Val Asn His Ser Leu Ser Phe Ile Ser Cys Pro Thr Ser Asp Ala Val Asn His Ser Leu Ser Phe Ile Ser

1490 1495 1490 1495

Asp Gly Asn Val Leu Ala Leu His Arg Leu Leu Trp Asn Asn Gln 1505 1510 1515 Asp Gly Asn Val Leu Ala Leu His Arg Leu Leu Trp Asn Asn Gln 1505 1510 1515

Glu Lys Ile Gly Gln Tyr Leu Ser Ser Asn Arg Asp His Lys Ala 1520 1525 1530 Glu Lys Ile Gly Gln Tyr Leu Ser Ser Asn Arg Asp His Lys Ala 1520 1525 1530

Val Gly Arg Arg Pro Phe Asp Lys Met Ala Thr Leu Leu Ala Tyr 1535 1540 1545 Val Gly Arg Arg Pro Phe Asp Lys Met Wing Thr Leu Leu Wing Tyr 1535 1540 1545

Leu Gly Pro Pro Glu His Lys Pro Val Ala Asp Thr His Trp Ser 1550 1555 1560 Leu Gly Pro Pro Glu His Lys Pro Val Wing Asp Thr His Trp Ser 1550 1555 1560

Ser Leu Asn Leu Thr Ser Ser Lys Phe Glu Glu Phe Met Thr Arg 1565 1570 1575 Be Leu Asn Leu Thr Be Ser Lys Phe Glu Glu Phe Met Thr Arg 1565 1570 1575

His Gln Val His Glu Lys Glu Glu Phe Lys Ala Leu Lys Thr Leu 1580 1585 1590 His Gln Val His Glu Lys Glu Glu Phe Lys Ala Leu Lys Thr Leu 1580 1585 1590

Ser Ile Phe Tyr Gln Ala Gly Thr Ser Lys Ala Gly Asn Pro Ile 1595 1600 1605 Ser Ile Phe Tyr Gln Ala Gly Thr Ser Lys Ala Gly Asn Pro Ile 1595 1600 1605

Phe Tyr Tyr Val Ala Arg Arg Phe Lys Thr Gly Gln Ile Asn Gly 1610 1615 1620 Phe Tyr Tyr Val Ala Arg Arg Phe Lys Thr Gly Gln Ile Asn Gly 1610 1615 1620

Asp Leu Leu Ile Tyr His Val Leu Leu Thr Leu Lys Pro Tyr Tyr 1625 1630 1635 Asp Leu Leu Ile Tyr His Val Leu Leu Thr Leu Lys Pro Tyr Tyr 1625 1630 1635

Ala Lys Pro Tyr Glu Ile Val Val Asp Leu Thr His Thr Gly Pro 1640 1645 1650 Wing Lys Pro Tyr Glu Ile Val Val Asp Leu Thr His Thr Gly Pro 1640 1645 1650

Ser Asn Arg Phe Lys Thr Asp Phe Leu Ser Lys Trp Phe Val Val 1655 1660 1665 Ser Asn Arg Phe Lys Thr Asp Phe Leu Ser Lys Trp Phe Val Val 1655 1660 1665

Phe Pro Gly Phe Ala Tyr Asp Asn Val Ser Ala Val Tyr Ile Tyr 1670 1675 1680 Phe Pro Gly Phe Ala Tyr Asp Asn Val Ser Ala Val Tyr Ile Tyr 1670 1675 1680

Asn Cys Asn Ser Trp Val Arg Glu Tyr Thr Lys Tyr His Glu Arg 1685 1690 1695 Asn Cys Asn Ser Trp Val Arg Glu Tyr Thr Lys Tyr His Glu Arg 1685 1690 1695

Leu Leu Thr Gly Leu Lys Gly Ser Lys Arg Leu Val Phe Ile Asp 1700 1705 1710 Leu Leu Thr Gly Leu Lys Gly Ser Lys Arg Leu Val Phe Ile Asp 1700 1705 1710

Cys Pro Gly Lys Leu Ala Glu His Ile Glu His Glu Gln Gln Lys 1715 1720 1725 Cys Pro Gly Lys Leu Ala Glu His Ile Glu His Glu Gln Gln Lys 1715 1720 1725

Leu Pro Ala Ala Thr Leu Ala Leu Glu Glu Asp Leu Lys Val Phe 1730 1735 1740 Leu Pro Wing Thr Wing Leu Wing Leu Glu Glu Asp Leu Lys Val Phe 1730 1735 1740

His Asn Ala Leu Lys Leu Ala His Lys Asp Thr Lys Val Ser Ile 1745 1750 1755 His Asn Ala Leu Lys Leu Ala His Lys Asp Thr Lys Val Ser Ile 1745 1750 1755

Lys Val Gly Ser Thr Ala Val Gln Val Thr Ser Ala Glu Arg Thr 1760 1765 1770 Lys Val Gly Ser Thr Ala Val Gln Val Thr Ser Ala Glu Arg Thr 1760 1765 1770

Lys Val Leu Gly Gln Ser Val Phe Leu Asn Asp Ile Tyr Tyr Ala 1775 1780 1785 Lys Val Leu Gly Gln Ser Val Phe Leu Asn Asp Ile Tyr Tyr Ala 1775 1780 1785

Ser Glu Ile Glu Glu Ile Cys Leu Val Asp Glu Asn Gln Phe Thr 1790 1795 1800 Ser Glu Ile Glu Glu Ile Cys Leu Val Asp Glu Asn Gln Phe Thr 1790 1795 1800

Leu Thr Ile Ala Asn Gln Gly Thr Pro Leu Thr Phe Met His Gln 1805 1810 1815 Leu Thr Ile Ala Asn Gln Gly Thr Pro Leu Thr Phe Met His Gln 1805 1810 1815

Glu Cys Glu Ala Ile Val Gln Ser Ile Ile His Ile Arg Thr Arg 1820 1825 1830 Trp Glu Leu Ser Gln Pro Asp Ser Ile Pro Gln His Thr Lys Ile 1835 1840 1845 Glu Cys Glu Wing Ile Val Gln Ser Ile Ile His Ile Arg Thr Arg 1820 1825 1830 Trp Glu Leu Ser Gln Pro Asp Ser Ile Pro Gln His Thr Lys Ile 1835 1840 1845

Arg Pro Lys Asp Val Pro Gly Thr Leu Leu Asn Ile Ala Leu Leu 1850 1855 1860 Arg Pro Lys Asp Val Pro Gly Thr Leu Leu Asn Ile Ala Leu Leu 1850 1855 1860

Asn Leu Gly Ser Ser Asp Pro Ser Leu Arg Ser Ala Ala Tyr Asn 1865 1870 1875 Asn Leu Gly Ser Be Asp Pro Ser Leu Arg Be Ala Wing Tyr Asn 1865 1870 1875

Leu Leu Cys Ala Leu Thr Cys Thr Phe Asn Leu Lys Ile Glu Gly 1880 1885 1890 Leu Leu Cys Ala Leu Thr Cys Thr Phe Asn Leu Lys Ile Glu Gly 1880 1885 1890

Gln Leu Leu Glu Thr Ser Gly Leu Cys Ile Pro Ala Asn Asn Thr 1895 1900 1905 Gln Leu Leu Glu Thr Ser Gly Leu Cys Ile Pro Wing Asn Asn Thr 1895 1900 1905

Leu Phe Ile Val Ser Ile Ser Lys Thr Leu Ala Ala Asn Glu Pro 1910 1915 1920 Leu Phe Ile Val Ser Ile Ser Lys Thr Leu Ala Wing Asn Glu Pro 1910 1915 1920

His Leu Thr Leu Glu Phe Leu Glu Glu Cys Ile Ser Gly Phe Ser 1925 1930 1935 His Leu Thr Leu Glu Phe Leu Glu Glu Cys Ile Ser Gly Phe Ser 1925 1930 1935

Lys Ser Ser Ile Glu Leu Lys His Leu Cys Leu Glu Tyr Met Thr 1940 1945 1950 Lys Ser Be Ile Glu Leu Lys His Leu Cys Leu Glu Tyr Met Thr 1940 1945 1950

Pro Trp Leu Ser Asn Leu Val Arg Phe Cys Lys His Asn Asp Asp 1955 1960 1965 Pro Trp Leu Ser Asn Leu Val Arg Phe Cys Lys His Asn Asp Asp 1955 1960 1965

Ala Lys Arg Gln Arg Val Thr Ala Ile Leu Asp Lys Leu Ile Thr 1970 1975 1980 Wing Lys Arg Gln Arg Val Thr Wing Ile Leu Asp Lys Leu Ile Thr 1970 1975 1980

Met Thr Ile Asn Glu Lys Gln Met Tyr Pro Ser Ile Gln Ala Lys 1985 1990 1995 Met Thr Ile Asn Glu Lys Gln Met Tyr Pro Ser Ile Gln Ala Lys 1985 1990 1995

Ile Trp Gly Ser Leu Gly Gln Ile Thr Asp Leu Leu Asp Val Val 2000 2005 2010 Ile Trp Gly Ser Leu Gly Gln Ile Thr Asp Leu Leu Asp Val Val 2000 2005 2010

Leu Asp Ser Phe Ile Lys Thr Ser Ala Thr Gly Gly Leu Gly Ser 2015 2020 2025 Leu Asp Ser Phe Ile Lys Thr Ser Ala Thr Gly Gly Leu Gly Ser 2015 2020 2025

Ile Lys Ala Glu Val Met Ala Asp Thr Ala Val Ala Leu Ala Ser 2030 2035 2040 Ile Lys Wing Glu Val Met Wing Asp Thr Wing Val Wing Leu Wing Ser 2030 2035 2040

Gly Asn Val Lys Leu Val Ser Ser Lys Val Ile Gly Arg Met Cys 2045 2050 2055 Gly Asn Val Lys Leu Val Ser Ser Lys Val Ile Gly Arg Met Cys 2045 2050 2055

Lys Ile Ile Asp Lys Thr Cys Leu Ser Pro Thr Pro Thr Leu Glu 2060 2065 2070 Lys Ile Ile Asp Lys Thr Cys Leu Ser Pro Thr Pro Thr Leu Glu 2060 2065 2070

Gln His Leu Met Trp Asp Asp Ile Ala Ile Leu Ala Arg Tyr Met 2075 2080 2085 Gln His Leu Met Trp Asp Asp Ile Ile Wing Leu Wing Arg Tyr Met 2075 2080 2085

Leu Met Leu Ser Phe Asn Asn Ser Leu Asp Val Ala Ala His Leu 2090 2095 2100 Leu Met Leu Ser Phe Asn Asn Ser Leu Asp Val Ala Ala His Leu 2090 2095 2100

Pro Tyr Leu Phe His Val Val Thr Phe Leu Val Ala Thr Gly Pro 2105 2110 2115 Pro Tyr Leu Phe His Val Val Thr Phe Leu Val Ala Thr Gly Pro 2105 2110 2115

Leu Ser Leu Arg Ala Ser Thr His Gly Leu Val Ile Asn Ile Ile 2120 2125 2130 Leu Ser Leu Arg Ala Ser Thr His Gly Leu Val Ile Asn Ile Ile 2120 2125 2130

His Ser Leu Cys Thr Cys Ser Gln Leu His Phe Ser Glu Glu Thr 2135 2140 2145 His Ser Leu Cys Thr Cys Ser Gln Leu His Phe Ser Glu Glu Thr 2135 2140 2145

Lys Gln Val Leu Arg Leu Ser Leu Thr Glu Phe Ser Leu Pro Lys 2150 2155 2160 Lys Gln Val Leu Arg Leu Ser Leu Thr Glu Phe Ser Leu Pro Lys 2150 2155 2160

Phe Tyr Leu Leu Phe Gly Ile Ser Lys Val Lys Ser Ala Ala Val 2165 2170 2175 Ile Ala Phe Arg Ser Ser Tyr Arg Asp Arg Ser Phe Ser Pro Gly 2180 2185 2190 Phe Tyr Leu Leu Phe Gly Ile Ser Lys Val Lys Ser Ala Ala Val 2165 2170 2175 Ile Ala Phe Arg Ser Ser Tyr Arg Asp Arg Ser Phe Ser Pro Gly 2180 2185 2190

Ser Tyr Glu Arg Glu Thr Phe Ala Leu Thr Ser Leu Glu Thr Val 2195 2200 2205 Ser Tyr Glu Arg Glu Thr Phe Ala Leu Thr Ser Leu Glu Thr Val 2195 2200 2205

Thr Glu Ala Leu Leu Glu Ile Met Glu Ala Cys Met Arg Asp Ile 2210 2215 2220 Thr Glu Ala Leu Leu Glu Ile Met Glu Ala Cys Met Arg Asp Ile 2210 2215 2220

Pro Thr Cys Lys Trp Leu Asp Gln Trp Thr Glu Leu Ala Gln Arg 2225 2230 2235 Pro Thr Cys Lys Trp Leu Asp Gln Trp Thr Glu Leu Wing Gln Arg 2225 2230 2235

Phe Ala Phe Gln Tyr Asn Pro Ser Leu Gln Pro Arg Ala Leu Val 2240 2245 2250 Phe Ala Phe Gln Tyr Asn Pro Ser Leu Gln Pro Arg Ala Leu Val 2240 2245 2250

Val Phe Gly Cys Ile Ser Lys Arg Val Ser His Gly Gln Ile Lys 2255 2260 2265 Val Phe Gly Cys Ile Ser Lys Arg Val Ser His Gly Gln Ile Lys 2255 2260 2265

Gln Ile Ile Arg Ile Leu Ser Lys Ala Leu Glu Ser Cys Leu Lys 2270 2275 2280 Gln Ile Ile Arg Ile Leu Ser Lys Ala Leu Glu Ser Cys Leu Lys 2270 2275 2280

Gly Pro Asp Thr Tyr Asn Ser Gln Val Leu Ile Glu Ala Thr Val 2285 2290 2295 Gly Pro Asp Thr Tyr Asn Ser Gln Val Leu Ile Glu Ala Thr Val 2285 2290 2295

Ile Ala Leu Thr Lys Leu Gln Pro Leu Leu Asn Lys Asp Ser Pro 2300 2305 2310 Ile Ala Leu Thr Lys Leu Gln Pro Leu Leu Asn Lys Asp Ser Pro 2300 2305 2310

Leu His Lys Ala Leu Phe Trp Val Ala Val Ala Val Leu Gln Leu 2315 2320 2325 Leu His Lys Wing Leu Phe Trp Val Wing Val Wing Val Leu Gln Leu 2315 2320 2325

Asp Glu Val Asn Leu Tyr Ser Ala Gly Thr Ala Leu Leu Glu Gln 2330 2335 2340 Asp Glu Val Asn Leu Tyr Ser Wing Gly Thr Wing Leu Leu Glu Gln 2330 2335 2340

Asn Leu His Thr Leu Asp Ser Leu Arg Ile Phe Asn Asp Lys Ser 2345 2350 2355 Asn Leu His Thr Leu Asp Ser Leu Arg Ile Phe Asn Asp Lys Ser 2345 2350 2355

Pro Glu Glu Val Phe Met Ala Ile Arg Asn Pro Leu Glu Trp His 2360 2365 2370 Pro Glu Glu Val Phe Met Wing Ile Arg Asn Pro Leu Glu Trp His 2360 2365 2370

Cys Lys Gln Met Asp His Phe Val Gly Leu Asn Phe Asn Ser Asn 2375 2380 2385 Cys Lys Gln Met Asp His Phe Val Gly Leu Asn Phe Asn Ser Asn 2375 2380 2385

Phe Asn Phe Ala Leu Val Gly His Leu Leu Lys Gly Tyr Arg His 2390 2395 2400 Phe Asn Phe Ala Leu Val Gly His Leu Leu Lys Gly Tyr Arg His 2390 2395 2400

Pro Ser Pro Ala Ile Val Ala Arg Thr Val Arg Ile Leu His Thr 2405 2410 2415 Pro Ser Pro Wing Ile Val Wing Arg Thr Val Arg Ile Leu His Thr 2405 2410 2415

Leu Leu Thr Leu Val Asn Lys His Arg Asn Cys Asp Lys Phe Glu 2420 2425 2430 Leu Leu Thr Leu Val Asn Lys His Arg Asn Cys Asp Lys Phe Glu 2420 2425 2430

Val Asn Thr Gln Ser Val Ala Tyr Leu Ala Ala Leu Leu Thr Val 2435 2440 2445 Val Asn Thr Gln Ser Val Wing Tyr Leu Wing Wing Leu Leu Thr Val 2435 2440 2445

Ser Glu Glu Val Arg Ser Arg Cys Ser Leu Lys His Arg Lys Ser 2450 2455 2460 Ser Glu Glu Val Arg Ser Arg Cys Ser Leu Lys His Arg Lys Ser 2450 2455 2460

Leu Leu Leu Thr Asp Ile Ser Met Glu Asn Val Pro Met Asp Thr 2465 2470 2475 Leu Leu Leu Thr Asp Ile Ser Met Glu Asn Val Pro Met Asp Thr 2465 2470 2475

Tyr Pro Ile His His Gly Asp Pro Ser Tyr Arg Thr Leu Lys Glu 2480 2485 2490 Tyr Pro Ile His His Gly Asp Pro Ser Tyr Arg Thr Leu Lys Glu 2480 2485 2490

Thr Gln Pro Trp Ser Ser Pro Lys Gly Ser Glu Gly Tyr Leu Ala 2495 2500 2505 Thr Gln Pro Trp Ser Ser Pro Lys Gly Ser Glu Gly Tyr Leu Ala 2495 2500 2505

Ala Thr Tyr Pro Thr Val Gly Gln Thr Ser Pro Arg Ala Arg Lys Wing Thr Tyr Pro Thr Val Gly Gln Thr Ser Pro Arg Wing Arg Lys

2510 2515 2510 2515

Ser Met Ser Leu Asp Met Gly Gln Pro Ser Gln Ala Asn Thr Lys 2525 2530 2535 Be Met Be Leu Asp Met Gly Gln Pro Ser Gln Wing Asn Thr Lys 2525 2530 2535

Lys Leu Leu Gly Thr Arg Lys Ser Phe Asp His Leu Ile Ser Asp 2540 2545 2550 Lys Leu Leu Gly Thr Arg Lys Ser Phe Asp His Leu Ile Ser Asp 2540 2545 2550

Thr Lys Ala Pro Lys Arg Gln Glu Met Glu Ser Gly Ile Thr Thr 2555 2560 2565 Thr Lys Ala Pro Lys Arg Gln Glu Met Glu Ser Gly Ile Thr Thr 2555 2560 2565

Pro Pro Lys Met Arg Arg Val Ala Glu Thr Asp Tyr Glu Met Glu 2570 2575 2580 Pro Pro Lys Met Arg Arg Val Wing Glu Thr Asp Tyr Glu Met Glu 2570 2575 2580

Thr Gln Arg Ile Ser Ser Ser Gln Gln His Pro His Leu Arg Lys 2585 2590 2595 Thr Gln Arg Ile Be Be Be Gln Gln His Pro His Leu Arg Lys 2585 2590 2595

Val Ser Val Ser Glu Ser Asn Val Leu Leu Asp Glu Glu Val Leu 2600 2605 2610 Val Ser Val Ser Glu Ser Asn Val Leu Leu Asp Glu Glu Val Leu 2600 2605 2610

Thr Asp Pro Lys Ile Gln Ala Leu Leu Leu Thr Val Leu Ala Thr 2615 2620 2625 Thr Asp Pro Lys Ile Gln Ala Leu Leu Leu Thr Val Leu Ala Thr 2615 2620 2625

Leu Val Lys Tyr Thr Thr Asp Glu Phe Asp Gln Arg Ile Leu Tyr 2630 2635 2640 Leu Val Lys Tyr Thr Thr Asp Glu Phe Asp Gln Arg Ile Leu Tyr 2630 2635 2640

Glu Tyr Leu Ala Glu Ala Ser Val Val Phe Pro Lys Val Phe Pro 2645 2650 2655 Glu Tyr Leu Wing Glu Ala Ser Val Val Phe Pro Lys Val Phe Pro 2645 2650 2655

Val Val His Asn Leu Leu Asp Ser Lys Ile Asn Thr Leu Leu Ser 2660 2665 2670 Val Val His Asn Leu Leu Asp Ser Lys Ile Asn Thr Leu Leu Ser 2660 2665 2670

Leu Cys Gln Asp Pro Asn Leu Leu Asn Pro Ile His Gly Ile Val 2675 2680 2685 Leu Cys Gln Asp Pro Asn Leu Leu Asn Pro Ile His Gly Ile Val 2675 2680 2685

Gln Ser Val Val Tyr His Glu Glu Ser Pro Pro Gln Tyr Gln Thr 2690 2695 2700 Gln Ser Val Val Tyr His Glu Glu Ser Pro Pro Gln Tyr Gln Thr 2690 2695 2700

Ser Tyr Leu Gln Ser Phe Gly Phe Asn Gly Leu Trp Arg Phe Ala 2705 2710 2715 Ser Tyr Leu Gln Ser Phe Gly Phe Asn Gly Leu Trp Arg Phe Ala 2705 2710 2715

Gly Pro Phe Ser Lys Gln Thr Gln Ile Pro Asp Tyr Ala Glu Leu 2720 2725 2730 Gly Pro Phe Ser Lys Gln Thr Gln Ile Pro Asp Tyr Ala Glu Leu 2720 2725 2730

Ile Val Lys Phe Leu Asp Ala Leu Ile Asp Thr Tyr Leu Pro Gly 2735 2740 2745 Ile Val Lys Phe Leu Asp Ala Leu Ile Asp Thr Tyr Leu Pro Gly 2735 2740 2745

Ile Asp Glu Glu Thr Ser Glu Glu Ser Leu Leu Thr Pro Thr Ser 2750 2755 2760 Ile Asp Glu Glu Thr Ser Glu Glu Ser Leu Leu Thr Pro Thr Ser 2750 2755 2760

Pro Tyr Pro Pro Ala Leu Gln Ser Gln Leu Ser Ile Thr Ala Asn 2765 2770 2775 Pro Tyr Pro Pro Wing Leu Gln Ser Gln Leu Ser Ile Thr Wing Asn 2765 2770 2775

Leu Asn Leu Ser Asn Ser Met Thr Ser Leu Ala Thr Ser Gln His 2780 2785 2790 Leu Asn Leu Ser Asn Ser Met Thr Ser Leu Ala Thr Ser Gln His 2780 2785 2790

Ser Pro Gly Ile Asp Lys Glu Asn Val Glu Leu Ser Pro Thr Thr 2795 2800 2805 Ser Pro Gly Ile Asp Lys Glu Asn Val Glu Leu Ser Pro Thr Thr 2795 2800 2805

Gly His Cys Asn Ser Gly Arg Thr Arg His Gly Ser Ala Ser Gln 2810 2815 2820 Gly His Cys Asn Ser Gly Arg Thr Arg His Gly Ser Ala Ser Gln 2810 2815 2820

Val Gln Lys Gln Arg Ser Ala Gly Ser Phe Lys Arg Asn Ser Ile 2825 2830 2835 Val Gln Lys Gln Arg Ser Wing Gly Ser Phe Lys Arg Asn Ser Ile 2825 2830 2835

Lys Lys Ile Val Lys Lys Ile Val

<210> 50 <210> 50

<211> 1089 <211> 1089

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 50 Met Gly Thr Ser His Pro Ala Phe Leu Val Leu Gly Cys Leu Leu 1 5 10 15 <400> 50 Met Gly Thr Ser His Pro Ala Phe Leu Val Leu Gly Cys Leu Leu 1 5 10 15

Thr Gly Leu Ser Leu Ile Leu Cys Gln Leu Ser Leu Pro Ser Ile 20 25 30 Thr Gly Leu Ser Leu Ile Leu Cys Gln Leu Ser Leu Pro Ser Ile 20 25 30

Leu Pro Asn Glu Asn Glu Lys Val Val Gln Leu Asn Ser Ser Phe 35 40 45 Leu Pro Asn Glu Asn Glu Lys Val Val Gln Leu Asn Ser Ser Phe 35 40 45

Ser Leu Arg Cys Phe Gly Glu Ser Glu Val Ser Trp Gln Tyr Pro 50 55 60 Ser Leu Arg Cys Phe Gly Glu Ser Glu Val Ser Trp Gln Tyr Pro 50 55 60

Met Ser Glu Glu Glu Ser Ser Asp Val Glu Ile Arg Asn Glu Glu 65 70 75 Met Ser Glu Glu Glu Ser Ser Asp Val Glu Ile Arg Asn Glu Glu 65 70 75

Asn Asn Ser Gly Leu Phe Val Thr Val Leu Glu Val Ser Ser Ala 80 85 90 Asn Asn Ser Gly Leu Phe Val Thr Val Leu Glu Val Ser Ser Ala 80 85 90

Ser Ala Ala His Thr Gly Leu Tyr Thr Cys Tyr Tyr Asn His Thr 95 100 105 Ser Ala Wing His Thr Gly Leu Tyr Thr Cys Tyr Tyr Asn His Thr 95 100 105

Gln Thr Glu Glu Asn Glu Leu Glu Gly Arg His Ile Tyr Ile Tyr 110 115 120 Gln Thr Glu Glu Asn Glu Leu Glu Gly Arg His Ile Tyr Ile Tyr 110 115 120

Val Pro Asp Pro Asp Val Ala Phe Val Pro Leu Gly Met Thr Asp 125 130 135 Val Pro Asp Pro Asp Val Ala Phe Val Pro Leu Gly Met Thr Asp 125 130 135

Tyr Leu Val Ile Val Glu Asp Asp Asp Ser Ala Ile Ile Pro Cys 140 145 150 Tyr Leu Val Ile Val Glu Asp Asp Asp Ser Ile Ile Ile Pro Cys 140 145 150

Arg Thr Thr Asp Pro Glu Thr Pro Val Thr Leu His Asn Ser Glu 155 160 165 Arg Thr Thr Asp Pro Glu Thr Pro Val Thr Leu His Asn Ser Glu 155 160 165

Gly Val Val Pro Ala Ser Tyr Asp Ser Arg Gln Gly Phe Asn Gly 170 175 180 Gly Val Val Pro Ala Ser Tyr Asp Ser Arg Gln Gly Phe Asn Gly 170 175 180

Thr Phe Thr Val Gly Pro Tyr Ile Cys Glu Ala Thr Val Lys Gly 185 190 195 Thr Phe Thr Val Gly Pro Tyr Ile Cys Glu Ala Thr Val Lys Gly 185 190 195

Lys Lys Phe Gln Thr Ile Pro Phe Asn Val Tyr Ala Leu Lys Ala 200 205 210 Lys Lys Phe Gln Thr Ile Pro Phe Asn Val Tyr Ala Leu Lys Ala 200 205 210

Thr Ser Glu Leu Asp Leu Glu Met Glu Ala Leu Lys Thr Val Tyr 215 220 225 Thr Ser Glu Leu Asp Leu Glu Met Glu Ala Leu Lys Thr Val Tyr 215 220 225

Lys Ser Gly Glu Thr Ile Val Val Thr Cys Ala Val Phe Asn Asn 230 235 240 Lys Ser Gly Glu Thr Ile Val Val Thr Cys Ala Val Phe Asn Asn 230 235 240

Glu Val Val Asp Leu Gln Trp Thr Tyr Pro Gly Glu Val Lys Gly 245 250 255 Glu Val Val Asp Leu Gln Trp Thr Tyr Pro Gly Glu Val Lys Gly 245 250 255

Lys Gly Ile Thr Met Leu Glu Glu Ile Lys Val Pro Ser Ile Lys 260 265 270 Lys Gly Ile Thr Met Leu Glu Glu Ile Lys Val Pro Ser Ile Lys 260 265 270

Leu Val Tyr Thr Leu Thr Val Pro Glu Ala Thr Val Lys Asp Ser 275 280 285 Leu Val Tyr Thr Leu Thr Val Pro Glu Ala Thr Val Lys Asp Ser 275 280 285

Gly Asp Tyr Glu Cys Ala Ala Arg Gln Ala Thr Arg Glu Val Lys 290 295 300 Gly Asp Tyr Glu Cys Wing Wing Arg Gln Wing Thr Arg Glu Val Lys 290 295 300

Glu Met Lys Lys Val Thr Ile Ser Val His Glu Lys Gly Phe Ile 305 310 315 Glu Ile Lys Pro Thr Phe Ser Gln Leu Glu Ala Val Asn Leu His 320 325 Glu Met Lys Lys Val Thr Ile Ser Val His Glu Lys Gly Phe Ile 305 310 315 Glu Ile Lys Pro Thr Phe Ser Gln Leu Glu Ala Val Asn Leu His 320 325

Glu Val Lys His Phe Val Val Glu Val Arg Ala Tyr Pro Pro Pro 335 340 345 Glu Val Lys His Phe Val Val Glu Val Arg Wing Tyr Pro Pro Pro 335 340 345

Arg Ile Ser Trp Leu Lys Asn Asn Leu Thr Leu Ile Glu Asn Leu 350 355 360 Arg Ile Ser Trp Leu Lys Asn Asn Leu Thr Leu Ile Glu Asn Leu 350 355 360

Thr Glu Ile Thr Thr Asp Val Glu Lys Ile Gln Glu Ile Arg Tyr 365 370 375 Thr Glu Ile Thr Thr Asp Val Glu Lys Ile Gln Glu Ile Arg Tyr 365 370 375

Arg Ser Lys Leu Lys Leu Ile Arg Ala Lys Glu Glu Asp Ser Gly 380 385 390 Arg Ser Lys Leu Lys Leu Ile Arg Ala Lys Glu Glu Asp Ser Gly 380 385 390

His Tyr Thr Ile Val Ala Gln Asn Glu Asp Ala Val Lys Ser Tyr 395 400 405 His Tyr Thr Ile Val Wing Gln Asn Glu Asp Wing Val Lys Ser Tyr 395 400 405

Thr Phe Glu Leu Leu Thr Gln Val Pro Ser Ser Ile Leu Asp Leu 410 415 420 Thr Phe Glu Leu Leu Thr Gln Val Pro Ser Ser Ile Leu Asp Leu 410 415 420

Val Asp Asp His His Gly Ser Thr Gly Gly Gln Thr Val Arg Cys 425 430 435 Val Asp Asp His His Gly Ser Thr Gly Gly Gln Thr Val Arg Cys 425 430 435

Thr Ala Glu Gly Thr Pro Leu Pro Asp Ile Glu Trp Met Ile Cys 440 445 450 Thr Wing Glu Gly Thr Pro Leu Pro Asp Ile Glu Trp Met Ile Cys 440 445 450

Lys Asp Ile Lys Lys Cys Asn Asn Glu Thr Ser Trp Thr Ile Leu 455 460 465 Lys Asp Ile Lys Lys Cys Asn Asn Glu Thr Ser Trp Thr Ile Leu 455 460 465

Ala Asn Asn Val Ser Asn Ile Ile Thr Glu Ile His Ser Arg Asp 470 475 480 Wing Asn Asn Val Ser Asn Ile Ile Thr Glu Ile His Ser Arg Asp 470 475 480

Arg Ser Thr Val Glu Gly Arg Val Thr Phe Ala Lys Val Glu Glu 485 490 495 Arg Ser Thr Val Glu Gly Arg Val Thr Phe Ala Lys Val Glu Glu 485 490 495

Thr Ile Ala Val Arg Cys Leu Ala Lys Asn Leu Leu Gly Ala Glu 500 505 510 Thr Ile Wing Val Arg Cys Leu Wing Lys Asn Leu Leu Gly Wing Glu 500 505 510

Asn Arg Glu Leu Lys Leu Val Ala Pro Thr Leu Arg Ser Glu Leu 515 520 525 Asn Arg Glu Leu Lys Leu Val Ala Pro Thr Leu Arg Ser Glu Leu 515 520 525

Thr Val Ala Ala Ala Val Leu Val Leu Leu Val Ile Val Ile Ile 530 535 540 Thr Val Wing Wing Val Val Leu Val Leu Leu Val Ile Val Ile Ile 530 535 540

Ser Leu Ile Val Leu Val Val Ile Trp Lys Gln Lys Pro Arg Tyr 545 550 555 Ser Leu Ile Val Leu Val Val Ile Trp Lys Gln Lys Pro Arg Tyr 545 550 555

Glu Ile Arg Trp Arg Val Ile Glu Ser Ile Ser Pro Asp Gly His 560 565 570 Glu Ile Arg Trp Arg Val Ile Glu Ser Ile Ser Pro Asp Gly His 560 565 570

Glu Tyr Ile Tyr Val Asp Pro Met Gln Leu Pro Tyr Asp Ser Arg 575 580 585 Glu Tyr Ile Tyr Val Asp Pro Met Gln Leu Pro Tyr Asp Ser Arg 575 580 585

Trp Glu Phe Pro Arg Asp Gly Leu Val Leu Gly Arg Val Leu Gly 590 595 600 Trp Glu Phe Pro Arg Asp Gly Leu Val Leu Gly Arg Val Leu Gly 590 595 600

Ser Gly Ala Phe Gly Lys Val Val Glu Gly Thr Ala Tyr Gly Leu 605 610 615 Ser Gly Ala Phe Gly Lys Val Val Glu Gly Thr Ala Tyr Gly Leu 605 610 615

Ser Arg Ser Gln Pro Val Met Lys Val Ala Val Lys Met Leu Lys 620 625 630 Ser Arg Ser Gln Pro Val Met Lys Val Ala Val Lys Met Leu Lys 620 625 630

Pro Thr Ala Arg Ser Ser Glu Lys Gln Ala Leu Met Ser Glu Leu 635 640 645 Pro Thr Ala Arg Ser Ser Glu Lys Gln Ala Leu Met Ser Glu Leu 635 640 645

Lys Ile Met Thr His Leu Gly Pro His Leu Asn Ile Val Asn Leu Lys Ile Met Thr His Leu Gly Pro His Leu Asn Ile Val Asn Leu

650 655 650 655

Leu Gly Ala Cys Thr Lys Ser Gly Pro Ile Tyr Ile Ile Thr Glu 665 670 675 Leu Gly Ala Cys Thr Lys Ser Gly Pro Ile Tyr Ile Ile Thr Glu 665 670 675

Tyr Cys Phe Tyr Gly Asp Leu Val Asn Tyr Leu His Lys Asn Arg 680 685 690 Tyr Cys Phe Tyr Gly Asp Leu Val Asn Tyr Leu His Lys Asn Arg 680 685 690

Asp Ser Phe Leu Ser His His Pro Glu Lys Pro Lys Lys Glu Leu 695 700 705 Asp Ser Phe Leu Ser His His Pro Glu Lys Pro Lys Lys Glu Leu 695 700 705

Asp Ile Phe Gly Leu Asn Pro Ala Asp Glu Ser Thr Arg Ser Tyr 710 715 720 Asp Ile Phe Gly Leu Asn Pro Wing Asp Glu Ser Thr Arg Ser Tyr 710 715 720

Val Ile Leu Ser Phe Glu Asn Asn Gly Asp Tyr Met Asp Met Lys 725 730 735 Val Ile Leu Ser Phe Glu Asn Asn Gly Asp Tyr Met Asp Met Lys 725 730 735

Gln Ala Asp Thr Thr Gln Tyr Val Pro Met Leu Glu Arg Lys Glu 740 745 750 Gln Wing Asp Thr Thr Gln Tyr Val Pro Met Leu Glu Arg Lys Glu 740 745 750

Val Ser Lys Tyr Ser Asp Ile Gln Arg Ser Leu Tyr Asp Arg Pro 755 760 765 Val Ser Lys Tyr Ser Asp Ile Gln Arg Ser Leu Tyr Asp Arg Pro 755 760 765

Ala Ser Tyr Lys Lys Lys Ser Met Leu Asp Ser Glu Val Lys Asn 770 775 780 Wing Ser Tyr Lys Lys Lys Ser Met Leu Asp Ser Glu Val Lys Asn 770 775 780

Leu Leu Ser Asp Asp Asn Ser Glu Gly Leu Thr Leu Leu Asp Leu 785 790 795 Leu Leu Be Asp Asp Asn Ser Glu Gly Leu Thr Leu Leu Asp Leu 785 790 795

Leu Ser Phe Thr Tyr Gln Val Ala Arg Gly Met Glu Phe Leu Ala 800 805 810 Leu Ser Phe Thr Tyr Gln Val Wing Arg Gly Met Glu Phe Leu Wing 800 805 810

Ser Lys Asn Cys Val His Arg Asp Leu Ala Ala Arg Asn Val Leu 815 820 825 Ser Lys Asn Cys Val His Arg Asp Leu Ala Wing Arg Asn Val Leu 815 820 825

Leu Ala Gln Gly Lys Ile Val Lys Ile Cys Asp Phe Gly Leu Ala 830 835 840 Leu Wing Gln Gly Lys Ile Val Lys Ile Cys Asp Phe Gly Leu Wing 830 835 840

Arg Asp Ile Met His Asp Ser Asn Tyr Val Ser Lys Gly Ser Thr 845 850 855 Arg Asp Ile Met His Asp Ser Asn Tyr Val Ser Lys Gly Ser Thr 845 850 855

Phe Leu Pro Val Lys Trp Met Ala Pro Glu Ser Ile Phe Asp Asn 860 865 870 Phe Leu Pro Val Lys Trp Met Wing Pro Glu Ser Ile Phe Asp Asn 860 865 870

Leu Tyr Thr Thr Leu Ser Asp Val Trp Ser Tyr Gly Ile Leu Leu 875 880 885 Leu Tyr Thr Thr Leu Ser Asp Val Trp Ser Tyr Gly Ile Leu Leu 875 880 885

Trp Glu Ile Phe Ser Leu Gly Gly Thr Pro Tyr Pro Gly Met Met 890 895 900 Trp Glu Ile Phe Ser Leu Gly Gly Thr Pro Tyr Pro Gly Met Met 890 895 900

Val Asp Ser Thr Phe Tyr Asn Lys Ile Lys Ser Gly Tyr Arg Met 905 910 915 Val Asp Ser Thr Phe Tyr Asn Lys Ile Lys Ser Gly Tyr Arg Met 905 910 915

Ala Lys Pro Asp His Ala Thr Ser Glu Val Tyr Glu Ile Met Val 920 925 930 Ala Lys Pro Asp His Ala Thr Ser Glu Val Tyr Glu Ile Met Val 920 925 930

Lys Cys Trp Asn Ser Glu Pro Glu Lys Arg Pro Ser Phe Tyr His 935 940 945 Lys Cys Trp Asn Ser Glu Pro Glu Lys Arg Pro Ser Phe Tyr His 935 940 945

Leu Ser Glu Ile Val Glu Asn Leu Leu Pro Gly Gln Tyr Lys Lys 950 955 960 Leu Ser Glu Ile Val Glu Asn Leu Leu Pro Gly Gln Tyr Lys Lys 950 955 960

Ser Tyr Glu Lys Ile His Leu Asp Phe Leu Lys Ser Asp His Pro 965 970 975 Ser Tyr Glu Lys Ile His Leu Asp Phe Leu Lys Ser Asp His Pro 965 970 975

Ala Val Ala Arg Met Arg Val Asp Ser Asp Asn Ala Tyr Ile Gly 980 985 Wing Val Wing Arg Met Arg Val Asp Ser Asp Asn Wing Tyr Ile Gly 980 985

Val Thr Tyr Lys Asn Glu Glu Asp Lys Leu Lys Asp Trp Glu Gly 995 1000 1005 Val Thr Tyr Lys Asn Glu Glu Asp Lys Leu Lys Asp Trp Glu Gly 995 1000 1005

Gly Leu Asp Glu Gln Arg Leu Ser Ala Asp Ser Gly Tyr Ile Ile 1010 1015 1020 Gly Leu Asp Glu Gln Arg Leu Ser Ala Asp Ser Gly Tyr Ile Ile 1010 1015 1020

Pro Leu Pro Asp Ile Asp Pro Val Pro Glu Glu Glu Asp Leu Gly 1025 1030 1035 Pro Leu Pro Asp Ile Asp Pro Val Pro Glu Glu Glu Asp Leu Gly 1025 1030 1035

Lys Arg Asn Arg His Ser Ser Gln Thr Ser Glu Glu Ser Ala Ile 1040 1045 1050 Lys Arg Asn Arg His Ser Ser Gln Thr Ser Glu Glu Ser Ala Ile 1040 1045 1050

Glu Thr Gly Ser Ser Ser Ser Thr Phe Ile Lys Arg Glu Asp Glu 1055 1060 1065 Glu Thr Gly Be Be Be Be Thr Phe Ile Lys Arg Glu Asp Glu 1055 1060 1065

Thr Ile Glu Asp Ile Asp Met Met Asp Asp Ile Gly Ile Asp Ser 1070 1075 1080 Thr Ile Glu Asp Ile Asp Met Met Asp Asp Ile Gly Ile Asp Ser 1070 1075 1080

Ser Asp Leu Val Glu Asp Ser Phe Leu 1085 Ser Asp Leu Val Glu Asp Ser Phe Leu 1085

<210> 51 <210> 51

<211> 1106 <211> 1106

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 51 Met Arg Leu Pro Gly Ala Met Pro Ala Leu Ala Leu Lys Gly Glu 1 5 10 15 <400> 51 Met Arg Leu Pro Gly Wing Met Pro Wing Leu Wing Leu Lys Gly Glu 1 5 10 15

Leu Leu Leu Leu Ser Leu Leu Leu Leu Leu Glu Pro Gln Ile Ser 20 25 30 Leu Leu Leu Leu Ser Leu Leu Leu Leu Leu Glu Pro Gln Ile Ser 20 25 30

Gln Gly Leu Val Val Thr Pro Pro Gly Pro Glu Leu Val Leu Asn 35 40 45 Gln Gly Leu Val Val Thr Pro Pro Gly Pro Glu Leu Val Leu Asn 35 40 45

Val Ser Ser Thr Phe Val Leu Thr Cys Ser Gly Ser Ala Pro Val 50 55 60 Val Ser Ser Thr Phe Val Leu Thr Cys Ser Gly Ser Ala Pro Val 50 55 60

Val Trp Glu Arg Met Ser Gln Glu Pro Pro Gln Glu Met Ala Lys 65 70 75 Val Trp Glu Arg Met Ser Gln Glu Pro Pro Gln Glu Met Ala Lys 65 70 75

Ala Gln Asp Gly Thr Phe Ser Ser Val Leu Thr Leu Thr Asn Leu 80 85 90 Gln Wing Asp Gly Thr Phe Ser Ser Val Leu Thr Leu Thr Asn Leu 80 85 90

Thr Gly Leu Asp Thr Gly Glu Tyr Phe Cys Thr His Asn Asp Ser 95 100 105 Thr Gly Leu Asp Thr Gly Glu Tyr Phe Cys Thr His Asn Asp Ser 95 100 105

Arg Gly Leu Glu Thr Asp Glu Arg Lys Arg Leu Tyr Ile Phe Val 110 115 120 Arg Gly Leu Glu Thr Asp Glu Arg Lys Arg Leu Tyr Ile Phe Val 110 115 120

Pro Asp Pro Thr Val Gly Phe Leu Pro Asn Asp Ala Glu Glu Leu 125 130 135 Pro Asp Pro Thr Val Gly Phe Leu Pro Asn Asp Wing Glu Glu Leu 125 130 135

Phe Ile Phe Leu Thr Glu Ile Thr Glu Ile Thr Ile Pro Cys Arg 140 145 150 Phe Ile Phe Leu Thr Glu Ile Thr Glu Ile Thr Ile Pro Cys Arg 140 145 150

Val Thr Asp Pro Gln Leu Val Val Thr Leu His Glu Lys Lys Gly 155 160 165 Val Thr Asp Pro Gln Leu Val Val Thr Leu His Glu Lys Lys Gly 155 160 165

Asp Val Ala Leu Pro Val Pro Tyr Asp His Gln Arg Gly Phe Ser 170 175 180 Asp Val Wing Leu Pro Val Pro Tyr Asp His Gln Arg Gly Phe Ser 170 175 180

Gly Ile Phe Glu Asp Arg Ser Tyr Ile Cys Lys Thr Thr Ile Gly 185 190 195 Gly Ile Phe Glu Asp Arg Ser Tyr Ile Cys Lys Thr Thr Ile Gly 185 190 195

Asp Arg Glu Val Asp Ser Asp Ala Tyr Tyr Val Tyr Arg Leu Gln 200 205 210 Asp Arg Glu Val Asp Ser Asp Ala Tyr Tyr Val Tyr Arg Leu Gln 200 205 210

Val Ser Ser Ile Asn Val Ser Val Asn Ala Val Gln Thr Val Val 215 220 225 Val Ser Be Ile Asn Val Ser Val Asn Ala Val Gln Thr Val Val 215 220 225

Arg Gln Gly Glu Asn Ile Thr Leu Met Cys Ile Val Ile Gly Asn 230 235 240 Arg Gln Gly Glu Asn Ile Thr Leu Met Cys Ile Val Ile Gly Asn 230 235 240

Glu Val Val Asn Phe Glu Trp Thr Tyr Pro Arg Lys Glu Ser Gly 245 250 255 Glu Val Val Asn Phe Glu Trp Thr Tyr Pro Arg Lys Glu Ser Gly 245 250 255

Arg Leu Val Glu Pro Val Thr Asp Phe Leu Leu Asp Met Pro Tyr 260 265 270 Arg Leu Val Glu Pro Val Thr Asp Phe Leu Leu Asp Met Pro Tyr 260 265 270

His Ile Arg Ser Ile Leu His Ile Pro Ser Ala Glu Leu Glu Asp 275 280 285 His Ile Arg Ser Ile Leu His Ile Pro Ser Ala Glu Leu Glu Asp 275 280 285

Ser Gly Thr Tyr Thr Cys Asn Val Thr Glu Ser Val Asn Asp His 290 295 300 Ser Gly Thr Tyr Thr Cys Asn Val Thr Glu Ser Val Asn Asp His 290 295 300

Gln Asp Glu Lys Ala Ile Asn Ile Thr Val Val Glu Ser Gly Tyr 305 310 315 Gln Asp Glu Lys Ile Wing Asn Ile Thr Val Val Glu Ser Gly Tyr 305 310 315

Val Arg Leu Leu Gly Glu Val Gly Thr Leu Gln Phe Ala Glu Leu 320 325 330 Val Arg Leu Leu Gly Glu Val Gly Thr Leu Gln Phe Ala Glu Leu 320 325 330

His Arg Ser Arg Thr Leu Gln Val Val Phe Glu Ala Tyr Pro Pro 335 340 345 His Arg Ser Arg Thr Leu Gln Val Val Phe Glu Ala Tyr Pro Pro 335 340 345

Pro Thr Val Leu Trp Phe Lys Asp Asn Arg Thr Leu Gly Asp Ser 350 355 360 Pro Thr Val Leu Trp Phe Lys Asp Asn Arg Thr Leu Gly Asp Ser 350 355 360

Ser Ala Gly Glu Ile Ala Leu Ser Thr Arg Asn Val Ser Glu Thr 365 370 375 Ser Ala Gly Glu Ile Ala Leu Ser Thr Arg Asn Val Ser Glu Thr 365 370 375

Arg Tyr Val Ser Glu Leu Thr Leu Val Arg Val Lys Val Ala Glu 380 385 390 Arg Tyr Val Ser Glu Leu Thr Leu Val Arg Val Lys Val Wing Glu 380 385 390

Ala Gly His Tyr Thr Met Arg Ala Phe His Glu Asp Ala Glu Val 395 400 405 Wing Gly His Tyr Thr Met Arg Wing Phe His Glu Asp Wing Glu Val 395 400 405

Gln Leu Ser Phe Gln Leu Gln Ile Asn Val Pro Val Arg Val Leu 410 415 420 Gln Leu Ser Phe Gln Leu Gln Ile Asn Val Pro Val Arg Val Leu 410 415 420

Glu Leu Ser Glu Ser His Pro Asp Ser Gly Glu Gln Thr Val Arg 425 430 435 Glu Leu Ser Glu Ser His Pro Asp Ser Gly Glu Gln Thr Val Arg 425 430 435

Cys Arg Gly Arg Gly Met Pro Gln Pro Asn Ile Ile Trp Ser Ala 440 445 450 Cys Arg Gly Arg Gly Met Pro Gln Pro Asn Ile Ile Trp Ser Ala 440 445 450

Cys Arg Asp Leu Lys Arg Cys Pro Arg Glu Leu Pro Pro Thr Leu 455 460 465 Cys Arg Asp Leu Lys Arg Cys Pro Arg Glu Leu Pro Pro Thr Leu 455 460 465

Leu Gly Asn Ser Ser Glu Glu Glu Ser Gln Leu Glu Thr Asn Val 470 475 480 Leu Gly Asn Ser Be Glu Glu Glu Ser Gln Leu Glu Thr Asn Val 470 475 480

Thr Tyr Trp Glu Glu Glu Gln Glu Phe Glu Val Val Ser Thr Leu 485 490 495 Thr Tyr Trp Glu Glu Glu Gln Glu Phe Glu Val Val Ser Thr Leu 485 490 495

Arg Leu Gln His Val Asp Arg Pro Leu Ser Val Arg Cys Thr Leu 500 505 510 Arg Leu Gln His Val Asp Arg Pro Leu Ser Val Arg Cys Thr Leu 500 505 510

Arg Asn Ala Val Gly Gln Asp Thr Gln Glu Val Ile Val Val Pro 515 520 525 Arg Asn Wing Val Gly Gln Asp Thr Gln Glu Val Ile Val Val Pro 515 520 525

His Ser Leu Pro Phe Lys Val Val Val Ile Ser Ala Ile Leu Ala 530 535 540 His Ser Leu Pro Phe Lys Val Val Val Ile Ser Ala Ile Leu Ala 530 535 540

Leu Val Val Leu Thr Ile Ile Ser Leu Ile Ile Leu Ile Met Leu Leu Val Val Leu Thr Ile Ile Ser Leu Ile Ile Leu Ile Met Leu

545 550 545 550

Trp Gln Lys Lys Pro Arg Tyr Glu Ile Arg Trp Lys Val Ile Glu 560 565 570 Trp Gln Lys Lys Pro Arg Tyr Glu Ile Arg Trp Lys Val Ile Glu 560 565 570

Ser Val Ser Ser Asp Gly His Glu Tyr Ile Tyr Val Asp Pro Met 575 580 585 Be Val Be Be Asp Gly His Glu Tyr Ile Tyr Val Asp Pro Met 575 580 585

Gln Leu Pro Tyr Asp Ser Thr Trp Glu Leu Pro Arg Asp Gln Leu 590 595 600 Gln Leu Pro Tyr Asp Ser Thr Trp Glu Leu Pro Arg Asp Gln Leu 590 595 600

Val Leu Gly Arg Thr Leu Gly Ser Gly Ala Phe Gly Gln Val Val 605 610 615 Val Leu Gly Arg Thr Leu Gly Ser Gly Ala Phe Gly Gln Val Val 605 610 615

Glu Ala Thr Ala His Gly Leu Ser His Ser Gln Ala Thr Met Lys 620 625 630 Glu Ala Thr Ala His Gly Leu Ser His Ser Gln Ala Thr Met Lys 620 625 630

Val Ala Val Lys Met Leu Lys Ser Thr Ala Arg Ser Ser Glu Lys 635 640 645 Val Ala Val Lys Met Leu Lys Ser Thr Ala Arg Ser Ser Glu Lys 635 640 645

Gln Ala Leu Met Ser Glu Leu Lys Ile Met Ser His Leu Gly Pro 650 655 660 Gln Ala Leu Met Ser Glu Leu Lys Ile Met Ser His Leu Gly Pro 650 655 660

His Leu Asn Val Val Asn Leu Leu Gly Ala Cys Thr Lys Gly Gly 665 670 675 His Leu Asn Val Val Asn Leu Leu Gly Ala Cys Thr Lys Gly Gly 665 670 675

Pro Ile Tyr Ile Ile Thr Glu Tyr Cys Arg Tyr Gly Asp Leu Val 680 685 690 Pro Ile Tyr Ile Ile Thr Glu Tyr Cys Arg Tyr Gly Asp Leu Val 680 685 690

Asp Tyr Leu His Arg Asn Lys His Thr Phe Leu Gln His His Ser 695 700 705 Asp Tyr Leu His Arg Asn Lys His Thr Phe Leu Gln His His Ser 695 700 705

Asp Lys Arg Arg Pro Pro Ser Ala Glu Leu Tyr Ser Asn Ala Leu 710 715 720 Asp Lys Arg Arg Pro Pro Ser Wing Glu Leu Tyr Ser Asn Wing Leu 710 715 720

Pro Val Gly Leu Pro Leu Pro Ser His Val Ser Leu Thr Gly Glu 725 730 735 Pro Val Gly Leu Pro Leu Pro Be His Val Ser Leu Thr Gly Glu 725 730 735

Ser Asp Gly Gly Tyr Met Asp Met Ser Lys Asp Glu Ser Val Asp 740 745 750 Ser Asp Gly Gly Tyr Met Asp Met Ser Lys Asp Glu Ser Val Asp 740 745 750

Tyr Val Pro Met Leu Asp Met Lys Gly Asp Val Lys Tyr Ala Asp 755 760 765 Tyr Val Pro Met Leu Asp Met Lys Gly Asp Val Lys Tyr Ala Asp 755 760 765

Ile Glu Ser Ser Asn Tyr Met Ala Pro Tyr Asp Asn Tyr Val Pro 770 775 780 Ile Glu Ser Ser Asn Tyr Met Ala Pro Tyr Asp Asn Tyr Val Pro 770 775 780

Ser Ala Pro Glu Arg Thr Cys Arg Ala Thr Leu Ile Asn Glu Ser 785 790 795 Ser Ala Pro Glu Arg Thr Cys Arg Ala Thr Leu Ile Asn Glu Ser 785 790 795

Pro Val Leu Ser Tyr Met Asp Leu Val Gly Phe Ser Tyr Gln Val 800 805 810 Pro Val Leu Ser Tyr Met Asp Leu Val Gly Phe Ser Tyr Gln Val 800 805 810

Ala Asn Gly Met Glu Phe Leu Ala Ser Lys Asn Cys Val His Arg 815 820 825 Wing Asn Gly Met Glu Phe Leu Wing Ser Lys Asn Cys Val His Arg 815 820 825

Asp Leu Ala Ala Arg Asn Val Leu Ile Cys Glu Gly Lys Leu Val 830 835 840 Asp Leu Wing Wing Arg Asn Val Leu Ile Cys Glu Gly Lys Leu Val 830 835 840

Lys Ile Cys Asp Phe Gly Leu Ala Arg Asp Ile Met Arg Asp Ser 845 850 855 Lys Ile Cys Asp Phe Gly Leu Ala Arg Asp Ile Met Arg Asp Ser 845 850 855

Asn Tyr Ile Ser Lys Gly Ser Thr Phe Leu Pro Leu Lys Trp Met 860 865 870 Asn Tyr Ile Ser Lys Gly Ser Thr Phe Leu Pro Leu Lys Trp Met 860 865 870

Ala Pro Glu Ser Ile Phe Asn Ser Leu Tyr Thr Thr Leu Ser Asp 875 880 Pro Glu Wing Ser Ile Phe Asn Ser Leu Tyr Thr Thr Leu Ser Asp 875 880

Val Trp Ser Phe Gly Ile Leu Leu Trp Glu Ile Phe Thr Leu Gly 890 895 900 Val Trp Ser Phe Gly Ile Leu Leu Trp Glu Ile Phe Thr Leu Gly 890 895 900

Gly Thr Pro Tyr Pro Glu Leu Pro Met Asn Glu Gln Phe Tyr Asn 905 910 915 Gly Thr Pro Tyr Pro Glu Leu Pro Met Asn Glu Gln Phe Tyr Asn 905 910 915

Ala Ile Lys Arg Gly Tyr Arg Met Ala Gln Pro Ala His Ala Ser 920 925 930 Wing Ile Lys Arg Gly Tyr Arg Met Wing Gln Pro Wing His Wing Ser 920 925 930

Asp Glu Ile Tyr Glu Ile Met Gln Lys Cys Trp Glu Glu Lys Phe 935 940 945 Asp Glu Ile Tyr Glu Ile Met Gln Lys Cys Trp Glu Glu Lys Phe 935 940 945

Glu Ile Arg Pro Pro Phe Ser Gln Leu Val Leu Leu Leu Glu Arg 950 955 960 Glu Ile Arg Pro Pro Phe Ser Gln Leu Val Leu Leu Leu Glu Arg 950 955 960

Leu Leu Gly Glu Gly Tyr Lys Lys Lys Tyr Gln Gln Val Asp Glu 965 970 975 Leu Leu Gly Glu Gly Tyr Lys Lys Lys Tyr Gln Gln Val Asp Glu 965 970 975

Glu Phe Leu Arg Ser Asp His Pro Ala Ile Leu Arg Ser Gln Ala 980 985 990 Glu Phe Leu Arg Ser Asp His Pro Ala Ile Leu Arg Ser Gln Ala 980 985 990

Arg Leu Pro Gly Phe His Gly Leu Arg Ser Pro Leu Asp Thr Ser 995 1000 1005 Arg Leu Pro Gly Phe His Gly Leu Arg Ser Pro Leu Asp Thr Ser 995 1000 1005

Ser Val Leu Tyr Thr Ala Val Gln Pro Asn Glu Gly Asp Asn Asp 1010 1015 1020 Ser Val Leu Tyr Thr Wing Val Gln Pro Asn Glu Gly Asp Asn Asp 1010 1015 1020

Tyr Ile Ile Pro Leu Pro Asp Pro Lys Pro Glu Val Ala Asp Glu 1025 1030 1035 Tyr Ile Ile Pro Leu Pro Asp Pro Lys Pro Glu Val Wing Asp Glu 1025 1030 1035

Gly Pro Leu Glu Gly Ser Pro Ser Leu Ala Ser Ser Thr Leu Asn 1040 1045 1050 Gly Pro Leu Glu Gly Ser Pro Be Leu Ala Be Ser Thr Leu Asn 1040 1045 1050

Glu Val Asn Thr Ser Ser Thr Ile Ser Cys Asp Ser Pro Leu Glu 1055 1060 1065 Glu Val Asn Thr Ser Ser Thr Ile Ser Cys Asp Ser Pro Leu Glu 1055 1060 1065

Pro Gln Asp Glu Pro Glu Pro Glu Pro Gln Leu Glu Leu Gln Val 1070 1075 1080 Pro Gln Asp Glu Pro Glu Pro Glu Pro Gln Leu Glu Leu Gln Val 1070 1075 1080

Glu Pro Glu Pro Glu Leu Glu Gln Leu Pro Asp Ser Gly Cys Pro 1085 1090 1095 Glu Pro Glu Pro Glu Leu Glu Gln Leu Pro Asp Ser Gly Cys Pro 1085 1090 1095

Ala Pro Arg Ala Glu Ala Glu Asp Ser Phe Leu 1100 1105 Pro Wing Arg Glu Wing Glu Wing Asp Ser Phe Leu 1100 1105

<210> 52 <210> 52

<211> 603 <211> 603

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 52 Met Ser Ala Ala Val Thr Ala Gly Lys Leu Ala Arg Ala Pro Ala 1 5 10 15 <400> 52 Met Ser Wing Wing Val Thr Wing Gly Lys Leu Wing Arg Wing Pro Wing 1 5 10 15

Asp Pro Gly Lys Ala Gly Val Pro Gly Val Ala Ala Pro Gly Ala 20 25 30 Asp Pro Gly Lys Wing Gly Val Pro Gly Val Wing Wing Pro Gly Wing 20 25 30

Pro Ala Ala Ala Pro Pro Ala Lys Glu Ile Pro Glu Val Leu Val 35 40 45 Pro Wing Wing Pro Wing Pro Wing Lys Glu Ile Pro Glu Val Leu Val 35 40 45

Asp Pro Arg Ser Arg Arg Arg Tyr Val Arg Gly Arg Phe Leu Gly 50 55 60 Asp Pro Arg Ser Arg Arg Arg Tyr Val Arg Gly Arg Phe Leu Gly 50 55 60

Lys Gly Gly Phe Ala Lys Cys Phe Glu Ile Ser Asp Ala Asp Thr 65 70 75 Lys Gly Gly Phe Ala Lys Cys Phe Glu Ile Ser Asp Ala Asp Thr 65 70 75

Lys Glu Val Phe Ala Gly Lys Ile Val Pro Lys Ser Leu Leu Leu 80 85 90 Lys Pro His Gln Arg Glu Lys Met Ser Met Glu Ile Ser Ile His 95 100 Lys Glu Val Phe Wing Gly Lys Ile Val Pro Lys Ser Leu Leu Leu 80 85 90 Lys Pro His Gln Arg Glu Lys Met Ser Met Glu Ile Ser Ile His 95 100

Arg Ser Leu Ala His Gln His Val Val Gly Phe His Gly Phe Phe 110 115 120 Arg Ser Leu Ala His Gln His Val Val Gly Phe His Gly Phe Phe 110 115 120

Glu Asp Asn Asp Phe Val Phe Val Val Leu Glu Leu Cys Arg Arg 125 130 135 Glu Asp Asn Asp Phe Val Phe Val Val Leu Glu Leu Cys Arg Arg 125 130 135

Arg Ser Leu Leu Glu Leu His Lys Arg Arg Lys Ala Leu Thr Glu 140 145 150 Arg Ser Leu Leu Glu Leu His Lys Arg Arg Lys Ala Leu Thr Glu 140 145 150

Pro Glu Ala Arg Tyr Tyr Leu Arg Gln Ile Val Leu Gly Cys Gln 155 160 165 Pro Glu Ala Arg Tyr Tyr Leu Arg Gln Ile Val Leu Gly Cys Gln 155 160 165

Tyr Leu His Arg Asn Arg Val Ile His Arg Asp Leu Lys Leu Gly 170 175 180 Tyr Leu His Arg Asn Arg Val Ile His Arg Asp Leu Lys Leu Gly 170 175 180

Asn Leu Phe Leu Asn Glu Asp Leu Glu Val Lys Ile Gly Asp Phe 185 190 195 Asn Leu Phe Leu Asn Glu Asp Leu Glu Val Lys Ile Gly Asp Phe 185 190 195

Gly Leu Ala Thr Lys Val Glu Tyr Asp Gly Glu Arg Lys Lys Thr 200 205 210 Gly Leu Wing Thr Lys Val Glu Tyr Asp Gly Glu Arg Lys Lys Thr 200 205 210

Leu Cys Gly Thr Pro Asn Tyr Ile Ala Pro Glu Val Leu Ser Lys 215 220 225 Leu Cys Gly Thr Pro Asn Tyr Ile Wing Pro Glu Val Leu Ser Lys 215 220 225

Lys Gly His Ser Phe Glu Val Asp Val Trp Ser Ile Gly Cys Ile 230 235 240 Lys Gly His Ser Phe Glu Val Asp Val Trp Ser Ile Gly Cys Ile 230 235 240

Met Tyr Thr Leu Leu Val Gly Lys Pro Pro Phe Glu Thr Ser Cys 245 250 255 Met Tyr Thr Leu Leu Val Gly Lys Pro Pro Phe Glu Thr Ser Cys 245 250 255

Leu Lys Glu Thr Tyr Leu Arg Ile Lys Lys Asn Glu Tyr Ser Ile 260 265 270 Leu Lys Glu Thr Tyr Leu Arg Ile Lys Lys Asn Glu Tyr Ser Ile 260 265 270

Pro Lys His Ile Asn Pro Val Ala Ala Ser Leu Ile Gln Lys Met 275 280 285 Pro Lys His Ile Asn Pro Val Ala Ala Ser Leu Ile Gln Lys Met 275 280 285

Leu Gln Thr Asp Pro Thr Ala Arg Pro Thr Ile Asn Glu Leu Leu 290 295 300 Leu Gln Thr Asp Pro Thr Ala Arg Pro Thr Ile Asn Glu Leu Leu 290 295 300

Asn Asp Glu Phe Phe Thr Ser Gly Tyr Ile Pro Ala Arg Leu Pro 305 310 315 Asn Asp Glu Phe Phe Thr Ser Gly Tyr Ile Pro Ala Arg Leu Pro 305 310 315

Ile Thr Cys Leu Thr Ile Pro Pro Arg Phe Ser Ile Ala Pro Ser 320 325 330 Ile Thr Cys Leu Thr Ile Pro Pro Arg Phe Ser Ile Ala Pro Ser 320 325 330

Ser Leu Asp Pro Ser Asn Arg Lys Pro Leu Thr Val Leu Asn Lys 335 340 345 Be Leu Asp Pro Be Asn Arg Lys Pro Leu Thr Val Leu Asn Lys 335 340 345

Gly Leu Glu Asn Pro Leu Pro Glu Arg Pro Arg Glu Lys Glu Glu 350 355 360 Gly Leu Glu Asn Pro Leu Pro Glu Arg Pro Arg Glu Lys Glu Glu 350 355 360

Pro Val Val Arg Glu Thr Gly Glu Val Val Asp Cys His Leu Ser 365 370 375 Pro Val Val Arg Glu Thr Gly Glu Val Val Asp Cys His Leu Ser 365 370 375

Asp Met Leu Gln Gln Leu His Ser Val Asn Ala Ser Lys Pro Ser 380 385 390 Asp Met Leu Gln Gln Leu His Ser Val Asn Ala Ser Lys Pro Ser 380 385 390

Glu Arg Gly Leu Val Arg Gln Glu Glu Ala Glu Asp Pro Ala Cys 395 400 405 Glu Arg Gly Leu Val Arg Gln Glu Glu Ala Glu Asp Pro Ala Cys 395 400 405

Ile Pro Ile Phe Trp Val Ser Lys Trp Val Asp Tyr Ser Asp Lys 410 415 420 Ile Pro Ile Phe Trp Val Ser Lys Trp Val Asp Tyr Ser Asp Lys 410 415 420

Tyr Gly Leu Gly Tyr Gln Leu Cys Asp Asn Ser Val Gly Val Leu Tyr Gly Leu Gly Tyr Gln Leu Cys Asp Asn Ser Val Gly Val Leu

425 430 435 425 430 435

Phe Asn Asp Ser Thr Arg Leu Ile Leu Tyr Asn Asp Gly Asp Ser 440 445 450 Phe Asn Asp Ser Thr Arg Leu Ile Leu Tyr Asn Asp Gly Asp Ser 440 445 450

Leu Gln Tyr Ile Glu Arg Asp Gly Thr Glu Ser Tyr Leu Thr Val 455 460 465 Leu Gln Tyr Ile Glu Arg Asp Gly Thr Glu Ser Tyr Leu Thr Val 455 460 465

Ser Ser His Pro Asn Ser Leu Met Lys Lys Ile Thr Leu Leu Lys 470 475 480 Ser Ser His Pro Asn Ser Leu Met Lys Lys Ile Thr Leu Leu Lys 470 475 480

Tyr Phe Arg Asn Tyr Met Ser Glu His Leu Leu Lys Ala Gly Ala 485 490 495 Tyr Phe Arg Asn Tyr Met Ser Glu His Leu Leu Lys Ala Gly Ala 485 490 495

Asn Ile Thr Pro Arg Glu Gly Asp Glu Leu Ala Arg Leu Pro Tyr 500 505 510 Asn Ile Thr Pro Arg Glu Gly Asp Glu Leu Ala Arg Leu Pro Tyr 500 505 510

Leu Arg Thr Trp Phe Arg Thr Arg Ser Ala Ile Ile Leu His Leu 515 520 525 Leu Arg Thr Trp Phe Arg Thr Arg Ser Ile Ile Leu His Leu 515 520 525

Ser Asn Gly Ser Val Gln Ile Asn Phe Phe Gln Asp His Thr Lys 530 535 540 Ser Asn Gly Ser Val Gln Ile Asn Phe Phe Gln Asp His Thr Lys 530 535 540

Leu Ile Leu Cys Pro Leu Met Ala Ala Val Thr Tyr Ile Asp Glu 545 550 555 Leu Ile Leu Cys Pro Leu Met Wing Wing Val Thr Tyr Ile Asp Glu 545 550 555

Lys Arg Asp Phe Arg Thr Tyr Arg Leu Ser Leu Leu Glu Glu Tyr 560 565 570 Lys Arg Asp Phe Arg Thr Tyr Arg Leu Ser Leu Leu Glu Glu Tyr 560 565 570

Gly Cys Cys Lys Glu Leu Ala Ser Arg Leu Arg Tyr Ala Arg Thr 575 580 585 Gly Cys Cys Lys Glu Leu Ala Ser Arg Leu Arg Tyr Ala Arg Thr 575 580 585

Met Val Asp Lys Leu Leu Ser Ser Arg Ser Ala Ser Asn Arg Leu 590 595 600 Met Val Asp Lys Leu Leu Be Be Arg Be Wing Be Asn Arg Leu 590 595 600

Lys Ala Ser Lys Ala Ser

<210> 53 <210> 53

<211> 631 <211> 631

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 53 Met Val Ser Lys Leu Ser Gln Leu Gln Thr Glu Leu Leu Ala Ala 1 5 10 15 <400> 53 Met Val Ser Lys Leu Ser Gln Leu Gln Thr Glu Leu Leu Wing 1 5 10 15

Leu Leu Glu Ser Gly Leu Ser Lys Glu Ala Leu Ile Gln Ala Leu 20 25 30 Leu Leu Glu Ser Gly Leu Ser Lys Glu Ala Leu Ile Gln Ala Leu 20 25 30

Gly Glu Pro Gly Pro Tyr Leu Leu Ala Gly Glu Gly Pro Leu Asp 35 40 45 Gly Glu Pro Gly Pro Tyr Leu Leu Wing Gly Glu Gly Pro Leu Asp 35 40 45

Lys Gly Glu Ser Cys Gly Gly Gly Arg Gly Glu Leu Ala Glu Leu 50 55 60 Lys Gly Glu Ser Cys Gly Gly Gly Arg Gly Glu Leu Wing Glu Leu 50 55 60

Pro Asn Gly Leu Gly Glu Thr Arg Gly Ser Glu Asp Glu Thr Asp 65 70 75 Pro Asn Gly Leu Gly Glu Thr Arg Gly Ser Glu Asp Glu Thr Asp 65 70 75

Asp Asp Gly Glu Asp Phe Thr Pro Pro Ile Leu Lys Glu Leu Glu 80 85 90 Asp Asp Gly Glu Asp Phe Thr Pro Pro Ile Leu Lys Glu Leu Glu 80 85 90

Asn Leu Ser Pro Glu Glu Ala Ala His Gln Lys Ala Val Val Glu 95 100 105 Asn Leu Ser Pro Glu Glu Wing His Gln Lys Wing Val Val Glu 95 100 105

Thr Leu Leu Gln Glu Asp Pro Trp Arg Val Ala Lys Met Val Lys 110 115 120 Ser Tyr Leu Gln Gln His Asn Ile Pro Gln Arg Glu Val Val Asp 125 130 Thr Leu Leu Gln Glu Asp Pro Trp Arg Val Ala Lys Met Val Lys 110 115 120 Ser Tyr Leu Gln Gln His Asn Ile Pro Gln Arg Glu Val Val Asp 125 130

Thr Thr Gly Leu Asn Gln Ser His Leu Ser Gln His Leu Asn Lys 140 145 150 Thr Thr Gly Leu Asn Gln Ser His Leu Ser Gln His Leu Asn Lys 140 145 150

Gly Thr Pro Met Lys Thr Gln Lys Arg Ala Ala Leu Tyr Thr Trp 155 160 165 Gly Thr Pro Met Lys Thr Gln Lys Arg Wing Wing Leu Tyr Thr Trp 155 160 165

Tyr Val Arg Lys Gln Arg Glu Val Ala Gln Gln Phe Thr His Ala 170 175 180 Tyr Val Arg Lys Gln Arg Glu Val Ala Gln Gln Phe Thr His Ala 170 175 180

Gly Gln Gly Gly Leu Ile Glu Glu Pro Thr Gly Asp Glu Leu Pro 185 190 195 Gly Gln Gly Gly Leu Ile Glu Glu Pro Thr Gly Asp Glu Leu Pro 185 190 195

Thr Lys Lys Gly Arg Arg Asn Arg Phe Lys Trp Gly Pro Ala Ser 200 205 210 Thr Lys Lys Gly Arg Arg Asn Arg Phe Lys Trp Gly Pro Wing Ser 200 205 210

Gln Gln Ile Leu Phe Gln Ala Tyr Glu Arg Gln Lys Asn Pro Ser 215 220 225 Gln Gln Ile Leu Phe Gln Wing Tyr Glu Arg Gln Lys Asn Pro Ser 215 220 225

Lys Glu Glu Arg Glu Thr Leu Val Glu Glu Cys Asn Arg Ala Glu 230 235 240 Lys Glu Glu Arg Glu Thr Leu Val Glu Glu Cys Asn Arg Ala Glu 230 235 240

Cys Ile Gln Arg Gly Val Ser Pro Ser Gln Ala Gln Gly Leu Gly 245 250 255 Cys Ile Gln Arg Gly Val Ser Pro Ser Gln Ala Gln Gly Leu Gly 245 250 255

Ser Asn Leu Val Thr Glu Val Arg Val Tyr Asn Trp Phe Ala Asn 260 265 270 Ser Asn Leu Val Thr Glu Val Arg Val Tyr Asn Trp Phe Ala Asn 260 265 270

Arg Arg Lys Glu Glu Ala Phe Arg His Lys Leu Ala Met Asp Thr 275 280 285 Arg Arg Lys Glu Glu Ala Phe Arg His Lys Leu Ala Met Asp Thr 275 280 285

Tyr Ser Gly Pro Pro Pro Gly Pro Gly Pro Gly Pro Ala Leu Pro 290 295 300 Tyr Ser Gly Pro Pro Pro Gly Pro Gly Pro Gly Pro Ala Leu Pro 290 295 300

Ala His Ser Ser Pro Gly Leu Pro Pro Pro Ala Leu Ser Pro Ser 305 310 315 Ala His Ser Ser Pro Gly Leu Pro Pro Pro Ala Leu Ser Pro Ser 305 310 315

Lys Val His Gly Val Arg Tyr Gly Gln Pro Ala Thr Ser Glu Thr 320 325 330 Lys Val His Gly Val Arg Tyr Gly Gln Pro Wing Thr Ser Glu Thr 320 325 330

Ala Glu Val Pro Ser Ser Ser Gly Gly Pro Leu Val Thr Val Ser 335 340 345 Wing Glu Val Pro Ser Ser Ser Gly Gly Pro Leu Val Thr Val Ser 335 340 345

Thr Pro Leu His Gln Val Ser Pro Thr Gly Leu Glu Pro Ser His 350 355 360 Thr Pro Leu His Gln Val Ser Pro Thr Gly Leu Glu Pro Ser His 350 355 360

Ser Leu Leu Ser Thr Glu Ala Lys Leu Val Ser Ala Ala Gly Gly 365 370 375 Ser Leu Leu Ser Thr Glu Ala Lys Leu Val Ser Ala Ala Gly Gly 365 370 375

Pro Leu Pro Pro Val Ser Thr Leu Thr Ala Leu His Ser Leu Glu 380 385 390 Pro Leu Pro Pro Val Ser Thr Leu Thr Ala Leu His Ser Leu Glu 380 385 390

Gln Thr Ser Pro Gly Leu Asn Gln Gln Pro Gln Asn Leu Ile Met 395 400 405 Gln Thr Ser Pro Gly Leu Asn Gln Gln Pro Gln Asn Leu Ile Met 395 400 405

Ala Ser Leu Pro Gly Val Met Thr Ile Gly Pro Gly Glu Pro Ala 410 415 420 Wing Ser Leu Pro Gly Val Met Thr Ile Gly Pro Gly Glu Pro Wing 410 415 420

Ser Leu Gly Pro Thr Phe Thr Asn Thr Gly Ala Ser Thr Leu Val 425 430 435 Ser Leu Gly Pro Thr Phe Thr Asn Thr Gly Ala Ser Thr Leu Val 425 430 435

Ile Gly Leu Ala Ser Thr Gln Ala Gln Ser Val Pro Val Ile Asn 440 445 450 Ile Gly Leu Wing Ser Thr Gln Wing Gln Ser Val Pro Val Ile Asn 440 445 450

Ser Met Gly Ser Ser Leu Thr Thr Leu Gln Pro Val Gln Phe Ser 455 460 Be Met Gly Ser Be Leu Thr Thr Leu Gln Pro Val Gln Phe Ser 455 460

Gln Pro Leu His Pro Ser Tyr Gln Gln Pro Leu Met Pro Pro Val 470 475 480 Gln Pro Leu His Pro Ser Tyr Gln Gln Pro Leu Met Pro Pro Val 470 475 480

Gln Ser His Val Thr Gln Ser Pro Phe Met Ala Thr Met Ala Gln 485 490 495 Gln Ser His Val Thr Gln Ser Pro Phe Met Wing Thr Met Wing Gln 485 490 495

Leu Gln Ser Pro His Ala Leu Tyr Ser His Lys Pro Glu Val Ala 500 505 510 Leu Gln Ser Pro His Ala Leu Tyr Ser His Lys Pro Glu Val Ala 500 505 510

Gln Tyr Thr His Thr Gly Leu Leu Pro Gln Thr Met Leu Ile Thr 515 520 525 Gln Tyr Thr His Thr Gly Leu Leu Pro Gln Thr Met Leu Ile Thr 515 520 525

Asp Thr Thr Asn Leu Ser Ala Leu Ala Ser Leu Thr Pro Thr Lys 530 535 540 Asp Thr Thr Asn Leu Ser Ala Leu Ala Ser Leu Thr Pro Thr Lys 530 535 540

Gln Val Phe Thr Ser Asp Thr Glu Ala Ser Ser Glu Ser Gly Leu 545 550 555 Gln Val Phe Thr Be Asp Thr Glu Ala Ser Ser Glu Ser Gly Leu 545 550 555

His Thr Pro Ala Ser Gln Ala Thr Thr Leu His Val Pro Ser Gln 560 565 570 His Thr Pro Ala Ser Gln Ala Thr Thr Leu His Val Pro Ser Gln 560 565 570

Asp Pro Ala Ser Ile Gln His Leu Gln Pro Ala His Arg Leu Ser 575 580 585 Asp Pro Ala Ser Ile Gln His Leu Gln Pro Ala His Arg Leu Ser 575 580 585

Ala Ser Pro Thr Val Ser Ser Ser Ser Leu Val Leu Tyr Gln Ser 590 595 600 Wing Be Pro Thr Val Be Be Be Be Leu Val Leu Tyr Gln Ser 590 595 600

Ser Asp Ser Ser Asn Gly Gln Ser His Leu Leu Pro Ser Asn His 605 610 615 Be Asp Be Be Asn Gly Gln Be His Leu Leu Pro Be Asn His 605 610 615

Ser Val Ile Glu Thr Phe Ile Ser Thr Gln Met Ala Ser Ser Ser 620 625 630 Ser Val Ile Glu Thr Phe Ile Ser Thr Gln Met Ala Ser Ser Ser 620 625 630

Gln Gln

<210> 54 <210> 54

<211> 393 <211> 393

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 54 Met Glu Glu Pro Gln Ser Asp Pro Ser Val Glu Pro Pro Leu Ser 1 5 10 15 <400> 54 Met Glu Glu Pro Gln Ser Asp Pro Ser Val Glu Pro Pro Leu Ser 1 5 10 15

Gln Glu Thr Phe Ser Asp Leu Trp Lys Leu Leu Pro Glu Asn Asn 20 25 30 Gln Glu Thr Phe Ser Asp Leu Trp Lys Leu Leu Pro Glu Asn Asn 20 25 30

Val Leu Ser Pro Leu Pro Ser Gln Ala Met Asp Asp Leu Met Leu 35 40 45 Val Leu Ser Pro Leu Pro Ser Gln Wing Met Asp Asp Leu Met Leu 35 40 45

Ser Pro Asp Asp Ile Glu Gln Trp Phe Thr Glu Asp Pro Gly Pro 50 55 60 Ser Pro Asp Asp Ile Glu Gln Trp Phe Thr Glu Asp Pro Gly Pro 50 55 60

Asp Glu Ala Pro Arg Met Pro Glu Ala Ala Pro Pro Val Ala Pro 65 70 75 Asp Glu Wing Pro Arg Met Pro Glu Wing Pro Wing Pro Val Wing Pro 65 70 75

Ala Pro Ala Ala Pro Thr Pro Ala Ala Pro Ala Pro Ala Pro Ser 80 85 90 Pro Wing Pro Wing Thr Pro Wing Pro Wing Pro Wing Pro Wing Ser 80 85 90

Trp Pro Leu Ser Ser Ser Val Pro Ser Gln Lys Thr Tyr Gln Gly 95 100 105 Trp Pro Leu Be Be Be Val Pro Be Gln Lys Thr Tyr Gln Gly 95 100 105

Ser Tyr Gly Phe Arg Leu Gly Phe Leu His Ser Gly Thr Ala Lys 110 115 120 Ser Tyr Gly Phe Arg Leu Gly Phe Leu His Ser Gly Thr Ala Lys 110 115 120

Ser Val Thr Cys Thr Tyr Ser Pro Ala Leu Asn Lys Met Phe Cys 125 130 135 Ser Val Thr Cys Thr Tyr Ser Pro Ala Leu Asn Lys Met Phe Cys 125 130 135

Gln Leu Ala Lys Thr Cys Pro Val Gln Leu Trp Val Asp Ser Thr 140 145 150 Gln Leu Wing Lys Thr Cys Pro Val Gln Leu Trp Val Asp Ser Thr 140 145 150

Pro Pro Pro Gly Thr Arg Val Arg Ala Met Ala Ile Tyr Lys Gln 155 160 165 Pro Pro Pro Gly Thr Arg Val Arg Met Wing Ile Tyr Lys Gln 155 160 165

Ser Gln His Met Thr Glu Val Val Arg Arg Cys Pro His His Glu 170 175 180 Ser Gln His Met Thr Glu Val Val Arg Arg Cys Pro His His Glu 170 175 180

Arg Cys Ser Asp Ser Asp Gly Leu Ala Pro Pro Gln His Leu Ile 185 190 195 Arg Cys Ser Asp Ser Asp Gly Leu Ala Pro Pro Gln His Leu Ile 185 190 195

Arg Val Glu Gly Asn Leu Arg Val Glu Tyr Leu Asp Asp Arg Asn 200 205 210 Arg Val Glu Gly Asn Leu Arg Val Glu Tyr Leu Asp Asp Arg Asn 200 205 210

Thr Phe Arg His Ser Val Val Val Pro Tyr Glu Pro Pro Glu Val 215 220 225 Thr Phe Arg His Ser Val Val Val Pro Tyr Glu Pro Pro Glu Val 215 220 225

Gly Ser Asp Cys Thr Thr Ile His Tyr Asn Tyr Met Cys Asn Ser 230 235 240 Gly Ser Asp Cys Thr Thr Ile His Tyr Asn Tyr Met Cys Asn Ser 230 235 240

Ser Cys Met Gly Gly Met Asn Arg Arg Pro Ile Leu Thr Ile Ile 245 250 255 Ser Cys Met Gly Gly Met Asn Arg Arg Pro Ile Leu Thr Ile Ile 245 250 255

Thr Leu Glu Asp Ser Ser Gly Asn Leu Leu Gly Arg Asn Ser Phe 260 265 270 Thr Leu Glu Asp Ser Ser Gly Asn Leu Leu Gly Arg Asn Ser Phe 260 265 270

Glu Val Arg Val Cys Ala Cys Pro Gly Arg Asp Arg Arg Thr Glu 275 280 285 Glu Val Arg Val Cys Ala Cys Pro Gly Arg Asp Arg Arg Thr Glu 275 280 285

Glu Glu Asn Leu Arg Lys Lys Gly Glu Pro His His Glu Leu Pro 290 295 300 Glu Glu Asn Leu Arg Lys Lys Gly Glu Pro His His Glu Leu Pro 290 295 300

Pro Gly Ser Thr Lys Arg Ala Leu Pro Asn Asn Thr Ser Ser Ser 305 310 315 Pro Gly Ser Thr Lys Arg Ala Leu Pro Asn Asn Thr Ser Ser Ser 305 310 315

Pro Gln Pro Lys Lys Lys Pro Leu Asp Gly Glu Tyr Phe Thr Leu 320 325 330 Pro Gln Pro Lys Lys Lys Pro Leu Asp Gly Glu Tyr Phe Thr Leu 320 325 330

Gln Ile Arg Gly Arg Glu Arg Phe Glu Met Phe Arg Glu Leu Asn 335 340 345 Gln Ile Arg Gly Arg Glu Arg Phe Glu Met Phe Arg Glu Leu Asn 335 340 345

Glu Ala Leu Glu Leu Lys Asp Ala Gln Ala Gly Lys Glu Pro Gly 350 355 360 Glu Wing Leu Glu Leu Lys Asp Wing Gln Wing Gly Lys Glu Pro Gly 350 355 360

Gly Ser Arg Ala His Ser Ser His Leu Lys Ser Lys Lys Gly Gln 365 370 375 Gly Ser Arg Ala His Ser Ser His Leu Lys Ser Lys Lys Gly Gln 365 370 375

Ser Thr Ser Arg His Lys Lys Leu Met Phe Lys Thr Glu Gly Pro 380 385 390 Ser Thr Ser Arg His Lys Lys Leu Met Phe Lys Thr Glu Gly Pro 380 385 390

Asp Ser Asp Asp Be Asp

<210> 55 <210> 55

<211> 764 <211> 764

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 55 Met Arg Pro Ala Asp Leu Leu Gln Leu Val Leu Leu Leu Asp Leu 1 5 10 15 <400> 55 Met Arg Pro Wing Asp Leu Leu Gln Leu Val Leu Leu Leu Asp Leu 1 5 10 15

Pro Arg Asp Leu Gly Gly Met Gly Cys Ser Ser Pro Pro Cys Glu 20 25 30 Cys His Gln Glu Glu Asp Phe Arg Val Thr Cys Lys Asp Ile Gln 35 40 Pro Arg Asp Leu Gly Gly Met Gly Cys Ser Ser Pro Pro Cys Glu 20 25 30 Cys His Gln Glu Glu Asp Phe Arg Val Thr Cys Lys Asp Ile Gln 35 40

Arg Ile Pro Ser Leu Pro Pro Ser Thr Gln Thr Leu Lys Leu Ile 50 55 60 Arg Ile Pro Ser Leu Pro Pro Ser Thr Gln Thr Leu Lys Leu Ile 50 55 60

Glu Thr His Leu Arg Thr Ile Pro Ser His Ala Phe Ser Asn Leu 65 70 75 Glu Thr His Leu Arg Thr Ile Pro Ser His Ala Phe Ser Asn Leu 65 70 75

Pro Asn Ile Ser Arg Ile Tyr Val Ser Ile Asp Val Thr Leu Gln 80 85 90 Pro Asn Ile Ser Arg Ile Tyr Val Ser Ile Asp Val Thr Leu Gln 80 85 90

Gln Leu Glu Ser His Ser Phe Tyr Asn Leu Ser Lys Val Thr His 95 100 105 Gln Leu Glu Ser His Ser Phe Tyr Asn Leu Ser Lys Val Thr His 95 100 105

Ile Glu Ile Arg Asn Thr Arg Asn Leu Thr Tyr Ile Asp Pro Asp 110 115 120 Ile Glu Ile Arg Asn Thr Arg Asn Leu Thr Tyr Ile Asp Pro Asp 110 115 120

Ala Leu Lys Glu Leu Pro Leu Leu Lys Phe Leu Gly Ile Phe Asn 125 130 135 Wing Leu Lys Glu Leu Pro Leu Leu Lys Phe Leu Gly Ile Phe Asn 125 130 135

Thr Gly Leu Lys Met Phe Pro Asp Leu Thr Lys Val Tyr Ser Thr 140 145 150 Thr Gly Leu Lys Met Phe Pro Asp Leu Thr Lys Val Tyr Ser Thr 140 145 150

Asp Ile Phe Phe Ile Leu Glu Ile Thr Asp Asn Pro Tyr Met Thr 155 160 165 Asp Ile Phe Phe Ile Leu Glu Ile Thr Asp Asn Pro Tyr Met Thr 155 160 165

Ser Ile Pro Val Asn Ala Phe Gln Gly Leu Cys Asn Glu Thr Leu 170 175 180 Ser Ile Pro Val Asn Ala Phe Gln Gly Leu Cys Asn Glu Thr Leu 170 175 180

Thr Leu Lys Leu Tyr Asn Asn Gly Phe Thr Ser Val Gln Gly Tyr 185 190 195 Thr Leu Lys Leu Tyr Asn Asn Gly Phe Thr Ser Val Gln Gly Tyr 185 190 195

Ala Phe Asn Gly Thr Lys Leu Asp Ala Val Tyr Leu Asn Lys Asn 200 205 210 Wing Phe Asn Gly Thr Lys Leu Asp Wing Val Tyr Leu Asn Lys Asn 200 205 210

Lys Tyr Leu Thr Val Ile Asp Lys Asp Ala Phe Gly Gly Val Tyr 215 220 225 Lys Tyr Leu Thr Val Ile Asp Lys Asp Ala Phe Gly Gly Val Tyr 215 220 225

Ser Gly Pro Ser Leu Leu Asp Val Ser Gln Thr Ser Val Thr Ala 230 235 240 Ser Gly Pro Ser Leu Leu Asp Val Ser Gln Thr Ser Val Thr Wing 230 235 240

Leu Pro Ser Lys Gly Leu Glu His Leu Lys Glu Leu Ile Ala Arg 245 250 255 Leu Pro Ser Lys Gly Leu Glu His Leu Lys Glu Leu Ile Wing Arg 245 250 255

Asn Thr Trp Thr Leu Lys Lys Leu Pro Leu Ser Leu Ser Phe Leu 260 265 270 Asn Thr Trp Thr Leu Lys Lys Leu Pro Leu Ser Leu Ser Phe Leu 260 265 270

His Leu Thr Arg Ala Asp Leu Ser Tyr Pro Ser His Cys Cys Ala 275 280 285 His Leu Thr Arg Ala Asp Leu Ser Tyr Pro Ser His Cys Cys Ala 275 280 285

Phe Lys Asn Gln Lys Lys Ile Arg Gly Ile Leu Glu Ser Leu Met 290 295 300 Phe Lys Asn Gln Lys Lys Ile Arg Gly Ile Leu Glu Ser Leu Met 290 295 300

Cys Asn Glu Ser Ser Met Gln Ser Leu Arg Gln Arg Lys Ser Val 305 310 315 Cys Asn Glu Ser Ser Met Gln Ser Leu Arg Gln Arg Lys Ser Val 305 310 315

Asn Ala Leu Asn Ser Pro Leu His Gln Glu Tyr Glu Glu Asn Leu 320 325 330 Asn Ala Leu Asn Ser Pro Leu His Gln Glu Tyr Glu Glu Asn Leu 320 325 330

Gly Asp Ser Ile Val Gly Tyr Lys Glu Lys Ser Lys Phe Gln Asp 335 340 345 Gly Asp Ser Ile Val Gly Tyr Lys Glu Lys Ser Lys Phe Gln Asp 335 340 345

Thr His Asn Asn Ala His Tyr Tyr Val Phe Phe Glu Glu Gln Glu 350 355 360 Thr His Asn Asn Ala His Tyr Tyr Val Phe Phe Glu Glu Gln Glu 350 355 360

Asp Glu Ile Ile Gly Phe Gly Gln Glu Leu Lys Asn Pro Gln Glu 365 370 Asp Glu Ile Ile Gly Phe Gly Gln Glu Leu Lys Asn Pro Gln Glu 365 370

Glu Thr Leu Gln Ala Phe Asp Ser His Tyr Asp Tyr Thr Ile Cys 380 385 Glu Thr Leu Gln Ala Phe Asp Ser His Tyr Asp Tyr Thr Ile Cys 380 385

Gly Asp Ser Glu Asp Met Val Cys Thr Pro Lys Ser Asp Glu Phe 395 400 405 Gly Asp Ser Glu Asp Met Val Cys Thr Pro Lys Ser Asp Glu Phe 395 400 405

Asn Pro Cys Glu Asp Ile Met Gly Tyr Lys Phe Leu Arg Ile Val 410 415 420 Asn Pro Cys Glu Asp Ile Met Gly Tyr Lys Phe Leu Arg Ile Val 410 415 420

Val Trp Phe Val Ser Leu Leu Ala Leu Leu Gly Asn Val Phe Val 425 430 435 Val Trp Phe Val Ser Leu Leu Ala Leu Leu Gly Asn Val Phe Val 425 430 435

Leu Leu Ile Leu Leu Thr Ser His Tyr Lys Leu Asn Val Pro Arg 440 445 450 Leu Leu Ile Leu Leu Thr Ser His Tyr Lys Leu Asn Val Pro Arg 440 445 450

Phe Leu Met Cys Asn Leu Ala Phe Ala Asp Phe Cys Met Gly Met 455 460 465 Phe Leu Met Cys Asn Leu Wing Phe Wing Asp Phe Cys Met Gly Met 455 460 465

Tyr Leu Leu Leu Ile Ala Ser Val Asp Leu Tyr Thr His Ser Glu 470 475 480 Tyr Leu Leu Leu Ile Ala Ser Val Asp Leu Tyr Thr His Ser Glu 470 475 480

Tyr Tyr Asn His Ala Ile Asp Trp Gln Thr Gly Pro Gly Cys Asn 485 490 495 Tyr Tyr Asn His Ala Ile Asp Trp Gln Thr Gly Pro Gly Cys Asn 485 490 495

Thr Ala Gly Phe Phe Thr Val Phe Ala Ser Glu Leu Ser Val Tyr 500 505 510 Thr Wing Gly Phe Phe Thr Val Phe Wing Ser Glu Leu Ser Val Tyr 500 505 510

Thr Leu Thr Val Ile Thr Leu Glu Arg Trp Tyr Ala Ile Thr Phe 515 520 525 Thr Leu Thr Val Ile Thr Leu Glu Arg Trp Tyr Ile Thr Phe 515 520 525

Ala Met Arg Leu Asp Arg Lys Ile Arg Leu Arg His Ala Cys Ala 530 535 540 Wing Met Arg Leu Asp Arg Lys Ile Arg Leu Arg His Wing Cys Wing 530 535 540

Ile Met Val Gly Gly Trp Val Cys Cys Phe Leu Leu Ala Leu Leu 545 550 555 Ile Met Val Gly Gly Trp Val Cys Cys Phe Leu Leu Ala Leu Leu 545 550 555

Pro Leu Val Gly Ile Ser Ser Tyr Ala Lys Val Ser Ile Cys Leu 560 565 570 Pro Leu Val Gly Ile Ser Be Tyr Ala Lys Val Ser Ile Cys Leu 560 565 570

Pro Met Asp Thr Glu Thr Pro Leu Ala Leu Ala Tyr Ile Val Phe 575 580 585 Pro Met Asp Thr Glu Thr Pro Leu Wing Leu Wing Tyr Ile Val Phe 575 580 585

Val Leu Thr Leu Asn Ile Val Ala Phe Val Ile Val Cys Cys Cys 590 595 600 Val Leu Thr Leu Asn Ile Val Ala Phe Val Ile Val Cys Cys Cys 590 595 600

Tyr Val Lys Ile Tyr Ile Thr Val Arg Asn Pro Gln Tyr Asn Pro 605 610 615 Tyr Val Lys Ile Tyr Ile Thr Val Arg Asn Pro Gln Tyr Asn Pro 605 610 615

Gly Asp Lys Asp Thr Lys Ile Ala Lys Arg Met Ala Val Leu Ile 620 625 630 Gly Asp Lys Asp Thr Lys Ile Wing Lys Arg Met Wing Val Leu Ile 620 625 630

Phe Thr Asp Phe Ile Cys Met Ala Pro Ile Ser Phe Tyr Ala Leu 635 640 645 Phe Thr Asp Phe Ile Cys Met Ala Pro Ile Ser Phe Tyr Ala Leu 635 640 645

Ser Ala Ile Leu Asn Lys Pro Leu Ile Thr Val Ser Asn Ser Lys 650 655 660 Ser Ala Ile Leu Asn Lys Pro Leu Ile Thr Val Ser Asn Ser Lys 650 655 660

Ile Leu Leu Val Leu Phe Tyr Pro Leu Asn Ser Cys Ala Asn Pro 665 670 675 Ile Leu Leu Val Leu Phe Tyr Pro Leu Asn Ser Cys Ala Asn Pro 665 670 675

Phe Leu Tyr Ala Ile Phe Thr Lys Ala Phe Gln Arg Asp Val Phe 680 685 690 Phe Leu Tyr Wing Ile Phe Thr Lys Wing Phe Gln Arg Asp Val Phe 680 685 690

Ile Leu Leu Ser Lys Phe Gly Ile Cys Lys Arg Gln Ala Gln Ala 695 700 705 Ile Leu Leu Ser Lys Phe Gly Ile Cys Lys Arg Gln Wing Gln Wing 695 700 705

Tyr Arg Gly Gln Arg Val Pro Pro Lys Asn Ser Thr Asp Ile Gln Tyr Arg Gly Gln Arg Val Pro Pro Lys Asn Ser Thr Asp Ile Gln

710 715 720 710 715 720

Val Gln Lys Val Thr His Glu Met Arg Gln Gly Leu His Asn Met 725 730 735 Val Gln Lys Val Thr His Glu Met Arg Gln Gly Leu His Asn Met 725 730 735

Glu Asp Val Tyr Glu Leu Ile Glu Asn Ser His Leu Thr Pro Lys 740 745 750 Glu Asp Val Tyr Glu Leu Ile Glu Asn Ser His Leu Thr Pro Lys 740 745 750

Lys Gln Gly Gln Ile Ser Glu Glu Tyr Met Gln Thr Val Leu 755 760 Lys Gln Gly Gln Ile Ser Glu Glu Tyr Met Gln Thr Val Leu 755 760

<210> 56 <210> 56

<211> 481 <211> 481

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 56 Met Asn Glu Val Ser Val Ile Lys Glu Gly Trp Leu His Lys Arg 1 5 10 15 <400> 56 Met Asn Glu Val Ser Val Ile Lys Glu Gly Trp Leu His Lys Arg 1 5 10 15

Gly Glu Tyr Ile Lys Thr Trp Arg Pro Arg Tyr Phe Leu Leu Lys 20 25 30 Gly Glu Tyr Ile Lys Thr Trp Arg Pro Arg Tyr Phe Leu Leu Lys 20 25 30

Ser Asp Gly Ser Phe Ile Gly Tyr Lys Glu Arg Pro Glu Ala Pro 35 40 45 Ser Asp Gly Ser Phe Ile Gly Tyr Lys Glu Arg Pro Glu Ala Pro 35 40 45

Asp Gln Thr Leu Pro Pro Leu Asn Asn Phe Ser Val Ala Glu Cys 50 55 60 Asp Gln Thr Leu Pro Pro Leu Asn Asn Phe Ser Val Ala Glu Cys 50 55 60

Gln Leu Met Lys Thr Glu Arg Pro Arg Pro Asn Thr Phe Val Ile 65 70 75 Gln Leu Met Lys Thr Glu Arg Pro Arg Pro Asn Thr Phe Val Ile 65 70 75

Arg Cys Leu Gln Trp Thr Thr Val Ile Glu Arg Thr Phe His Val 80 85 90 Arg Cys Leu Gln Trp Thr Thr Val Ile Glu Arg Thr Phe His Val 80 85 90

Asp Ser Pro Asp Glu Arg Glu Glu Trp Met Arg Ala Ile Gln Met 95 100 105 Asp Ser Pro Asp Glu Arg Glu Glu Trp Met Arg Ile Gln Met 95 100 105

Val Ala Asn Ser Leu Lys Gln Arg Ala Pro Gly Glu Asp Pro Met 110 115 120 Val Wing Asn Ser Leu Lys Gln Arg Wing Pro Gly Glu Asp Pro Met 110 115 120

Asp Tyr Lys Cys Gly Ser Pro Ser Asp Ser Ser Thr Thr Glu Glu 125 130 135 Asp Tyr Lys Cys Gly Ser Pro Ser Asp Ser Ser Thr Thr Glu Glu 125 130 135

Met Glu Val Ala Val Ser Lys Ala Arg Ala Lys Val Thr Met Asn 140 145 150 Met Glu Val Wing Val Ser Lys Wing Arg Wing Lys Val Thr Met Asn 140 145 150

Asp Phe Asp Tyr Leu Lys Leu Leu Gly Lys Gly Thr Phe Gly Lys 155 160 165 Asp Phe Asp Tyr Leu Lys Leu Leu Gly Lys Gly Thr Phe Gly Lys 155 160 165

Val Ile Leu Val Arg Glu Lys Ala Thr Gly Arg Tyr Tyr Ala Met 170 175 180 Val Ile Leu Val Arg Glu Lys Wing Thr Gly Arg Tyr Tyr Wing Met 170 175 180

Lys Ile Leu Arg Lys Glu Val Ile Ile Ala Lys Asp Glu Val Ala 185 190 195 Lys Ile Leu Arg Lys Glu Val Ile Ile Ala Lys Asp Glu Val Ala 185 190 195

His Thr Val Thr Glu Ser Arg Val Leu Gln Asn Thr Arg His Pro 200 205 210 His Thr Val Thr Glu Ser Arg Val Leu Gln Asn Thr Arg His Pro 200 205 210

Phe Leu Thr Ala Leu Lys Tyr Ala Phe Gln Thr His Asp Arg Leu 215 220 225 Phe Leu Thr Ala Leu Lys Tyr Ala Phe Gln Thr His Asp Arg Leu 215 220 225

Cys Phe Val Met Glu Tyr Ala Asn Gly Gly Glu Leu Phe Phe His 230 235 240 Cys Phe Val Met Glu Tyr Ala Asn Gly Gly Glu Leu Phe Phe His 230 235 240

Leu Ser Arg Glu Arg Val Phe Thr Glu Glu Arg Ala Arg Phe Tyr 245 250 255 Leu Ser Arg Glu Arg Val Phe Thr Glu Glu Arg Ala Arg Phe Tyr 245 250 255

Gly Ala Glu Ile Val Ser Ala Leu Glu Tyr Leu His Ser Arg Asp 260 265 270 Gly Ala Glu Ile Val Ser Ala Leu Glu Tyr Leu His Ser Arg Asp 260 265 270

Val Val Tyr Arg Asp Ile Lys Leu Glu Asn Leu Met Leu Asp Lys 275 280 285 Val Val Tyr Arg Asp Ile Lys Leu Glu Asn Leu Met Leu Asp Lys 275 280 285

Asp Gly His Ile Lys Ile Thr Asp Phe Gly Leu Cys Lys Glu Gly 290 295 300 Asp Gly His Ile Lys Ile Thr Asp Phe Gly Leu Cys Lys Glu Gly 290 295 300

Ile Ser Asp Gly Ala Thr Met Lys Thr Phe Cys Gly Thr Pro Glu 305 310 315 Ile Ser Asp Gly Ala Thr Met Lys Thr Phe Cys Gly Thr Pro Glu 305 310 315

Tyr Leu Ala Pro Glu Val Leu Glu Asp Asn Asp Tyr Gly Arg Ala 320 325 330 Tyr Leu Wing Pro Glu Val Leu Glu Asp Asn Asp Tyr Gly Arg Wing 320 325 330

Val Asp Trp Trp Gly Leu Gly Val Val Met Tyr Glu Met Met Cys 335 340 345 Val Asp Trp Trp Gly Leu Gly Val Val Met Tyr Glu Met Met Cys 335 340 345

Gly Arg Leu Pro Phe Tyr Asn Gln Asp His Glu Arg Leu Phe Glu 350 355 360 Gly Arg Leu Pro Phe Tyr Asn Gln Asp His Glu Arg Leu Phe Glu 350 355 360

Leu Ile Leu Met Glu Glu Ile Arg Phe Pro Arg Thr Leu Ser Pro 365 370 375 Leu Ile Leu Met Glu Glu Ile Arg Phe Pro Arg Thr Leu Ser Pro 365 370 375

Glu Ala Lys Ser Leu Leu Ala Gly Leu Leu Lys Lys Asp Pro Lys 380 385 390 Glu Ala Lys Ser Leu Leu Ala Gly Leu Leu Lys Lys Asp Pro Lys 380 385 390

Gln Arg Leu Gly Gly Gly Pro Ser Asp Ala Lys Glu Val Met Glu 395 400 405 Gln Arg Leu Gly Gly Gly Pro Ser Asp Ala Lys Glu Val Met Glu 395 400 405

His Arg Phe Phe Leu Ser Ile Asn Trp Gln Asp Val Val Gln Lys 410 415 420 His Arg Phe Phe Leu Ser Ile Asn Trp Gln Asp Val Val Gln Lys 410 415 420

Lys Leu Leu Pro Pro Phe Lys Pro Gln Val Thr Ser Glu Val Asp 425 430 435 Lys Leu Leu Pro Pro Phe Lys Pro Gln Val Thr Ser Glu Val Asp 425 430 435

Thr Arg Tyr Phe Asp Asp Glu Phe Thr Ala Gln Ser Ile Thr Ile 440 445 450 Thr Arg Tyr Phe Asp Asp Glu Phe Thr Wing Gln Ser Ile Thr Ile 440 445 450

Thr Pro Pro Asp Arg Tyr Asp Ser Leu Gly Leu Leu Glu Leu Asp 455 460 465 Thr Pro Pro Asp Arg Tyr Asp Ser Leu Gly Leu Leu Glu Leu Asp 455 460 465

Gln Arg Thr His Phe Pro Gln Phe Ser Tyr Ser Ala Ser Ile Arg 470 475 480 Gln Arg Thr His Phe Pro Gln Phe Ser Tyr Ser Ala Ser Ile Arg 470 475 480

Glu Glu

<210> 57 <210> 57

<211> 275 <211> 275

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 57 Met Arg Arg Leu Thr Val Asp Asp Phe Glu Ile Gly Arg Pro Leu 1 5 10 15 <400> 57 Met Arg Arg Leu Thr Val Asp Asp Phe Glu Ile Gly Arg Pro Leu 1 5 10 15

Gly Lys Gly Lys Phe Gly Asn Val Tyr Leu Ala Arg Leu Lys Glu 20 25 30 Gly Lys Gly Lys Phe Gly Asn Val Tyr Leu Ala Arg Leu Lys Glu 20 25 30

Ser His Phe Ile Val Ala Leu Lys Val Leu Phe Lys Ser Gln Ile 35 40 45 Be His Phe Ile Val Ala Leu Lys Val Leu Phe Lys Ser Gln Ile 35 40 45

Glu Lys Glu Gly Leu Glu His Gln Leu Arg Arg Glu Ile Glu Ile 50 55 60 Glu Lys Glu Gly Leu Glu His Gln Leu Arg Arg Glu Ile Glu Ile 50 55 60

Gln Ala His Leu Gln His Pro Asn Ile Leu Arg Leu Tyr Asn Tyr 65 70 75 Gln Ala His Leu Gln His Pro Asn Ile Leu Arg Leu Tyr Asn Tyr 65 70 75

Phe His Asp Ala Arg Arg Val Tyr Leu Ile Leu Glu Tyr Ala Pro 80 85 90 Phe His Asp Ala Arg Arg Val Tyr Leu Ile Leu Glu Tyr Ala Pro 80 85 90

Arg Gly Glu Leu Tyr Lys Glu Leu Gln Lys Ser Glu Lys Leu Asp 95 100 105 Arg Gly Glu Leu Tyr Lys Glu Leu Gln Lys Ser Glu Lys Leu Asp 95 100 105

Glu Gln Arg Thr Ala Thr Ile Ile Glu Glu Val Ala Asp Ala Leu 110 115 120 Glu Gln Arg Thr Wing Thr Ile Ile Glu Glu Val Wing Asp Wing Leu 110 115 120

Thr Tyr Cys His Asp Lys Lys Val Ile His Arg Asp Ile Lys Pro 125 130 135 Thr Tyr Cys His Asp Lys Lys Val Ile His Arg Asp Ile Lys Pro 125 130 135

Glu Asn Leu Leu Leu Gly Phe Arg Gly Glu Val Lys Ile Ala Asp 140 145 150 Glu Asn Leu Leu Leu Gly Phe Arg Gly Glu Val Lys Ile Wing Asp 140 145 150

Phe Gly Trp Ser Val His Thr Pro Leu Pro Glu Arg Lys Thr Met 155 160 165 Phe Gly Trp Ser Val His Thr Pro Leu Pro Glu Arg Lys Thr Met 155 160 165

Cys Gly Thr Leu Asp Tyr Leu Pro Pro Glu Met Ile Glu Gly Arg 170 175 180 Cys Gly Thr Leu Asp Tyr Leu Pro Pro Glu Met Ile Glu Gly Arg 170 175 180

Thr Tyr Asp Glu Lys Val Asp Leu Trp Cys Ile Gly Val Leu Cys 185 190 195 Thr Tyr Asp Glu Lys Val Asp Leu Trp Cys Ile Gly Val Leu Cys 185 190 195

Tyr Glu Leu Leu Val Gly Tyr Pro Pro Phe Glu Ser Ala Ser His 200 205 210 Tyr Glu Leu Leu Val Gly Tyr Pro Pro Phe Glu Ser Ala Ser His 200 205 210

Ser Glu Thr Tyr Arg Arg Ile Leu Lys Val Asp Val Arg Phe Pro 215 220 225 Ser Glu Thr Tyr Arg Arg Ile Leu Lys Val Asp Val Arg Phe Pro 215 220 225

Leu Ser Met Pro Leu Gly Ala Arg Asp Leu Ile Ser Arg Leu Leu 230 235 240 Leu Ser Met Pro Leu Gly Ala Arg Asp Leu Ile Ser Arg Leu Leu 230 235 240

Arg Tyr Gln Pro Leu Glu Arg Leu Pro Leu Ala Gln Ile Leu Lys 245 250 255 Arg Tyr Gln Pro Leu Glu Arg Leu Pro Leu Gln Wing Ile Leu Lys 245 250 255

His Pro Trp Val Gln Ala His Ser Arg Arg Val Leu Pro Pro Cys 260 265 270 His Pro Trp Val Gln Wing His Ser Arg Arg Val Leu Pro Pro Cys 260 265 270

Ala Gln Met Ala Ser 275 Gln Wing Met Wing Ser 275

<210> 58 <210> 58

<211> 233 <211> 233

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 58 Met Ser Gln Ser Asn Arg Glu Leu Val Val Asp Phe Leu Ser Tyr 1 5 10 15 <400> 58 Met Ser Gln Ser Asn Arg Glu Leu Val Val Asp Phe Leu Ser Tyr 1 5 10 15

Lys Leu Ser Gln Lys Gly Tyr Ser Trp Ser Gln Phe Ser Asp Val 20 25 30 Lys Leu Ser Gln Lys Gly Tyr Ser Trp Ser Gln Phe Ser Asp Val 20 25 30

Glu Glu Asn Arg Thr Glu Ala Pro Glu Gly Thr Glu Ser Glu Met 35 40 45 Glu Glu Asn Arg Thr Glu Ala Pro Glu Gly Thr Glu Ser Glu Met 35 40 45

Glu Thr Pro Ser Ala Ile Asn Gly Asn Pro Ser Trp His Leu Ala 50 55 60 Glu Thr Pro Ser Wing Ile Asn Gly Asn Pro Ser Trp His Leu Ala 50 55 60

Asp Ser Pro Ala Val Asn Gly Ala Thr Gly His Ser Ser Ser Leu 65 70 75 Asp Ser Pro Ala Val Asn Gly Ala Thr Gly His Ser Ser Ser Leu 65 70 75

Asp Ala Arg Glu Val Ile Pro Met Ala Ala Val Lys Gln Ala Leu 80 85 90 Asp Wing Arg Glu Val Ile Pro Met Wing Wing Val Lys Gln Wing Leu 80 85 90

Arg Glu Ala Gly Asp Glu Phe Glu Leu Arg Tyr Arg Arg Ala Phe 95 100 105 Arg Glu Ala Gly Asp Glu Phe Glu Leu Arg Tyr Arg Arg Ala Phe 95 100 105

Ser Asp Leu Thr Ser Gln Leu His Ile Thr Pro Gly Thr Ala Tyr 110 115 120 Ser Asp Leu Thr Ser Gln Leu His Ile Thr Pro Gly Thr Ala Tyr 110 115 120

Gln Ser Phe Glu Gln Val Val Asn Glu Leu Phe Arg Asp Gly Val 125 130 135 Gln Ser Phe Glu Gln Val Val Asn Glu Leu Phe Arg Asp Gly Val 125 130 135

Asn Trp Gly Arg Ile Val Ala Phe Phe Ser Phe Gly Gly Ala Leu 140 145 150 Asn Trp Gly Arg Ile Val Ala Phe Phe Ser Phe Gly Gly Ala Leu 140 145 150

Cys Val Glu Ser Val Asp Lys Glu Met Gln Val Leu Val Ser Arg 155 160 165 Cys Val Glu Ser Val Asp Lys Glu Met Gln Val Leu Val Ser Arg 155 160 165

Ile Ala Ala Trp Met Ala Thr Tyr Leu Asn Asp His Leu Glu Pro 170 175 180 Ile Wing Wing Trp Met Wing Thr Tyr Leu Asn Asp His Leu Glu Pro 170 175 180

Trp Ile Gln Glu Asn Gly Gly Trp Asp Thr Phe Val Glu Leu Tyr 185 190 195 Trp Ile Gln Glu Asn Gly Gly Trp Asp Thr Phe Val Glu Leu Tyr 185 190 195

Gly Asn Asn Ala Ala Ala Glu Ser Arg Lys Gly Gln Glu Arg Phe 200 205 210 Gly Asn Asn Wing Wing Glu Ser Arg Lys Gly Gln Glu Arg Phe 200 205 210

Asn Arg Trp Phe Leu Thr Gly Met Thr Val Ala Gly Val Val Leu 215 220 225 Asn Arg Trp Phe Leu Thr Gly Met Thr Val Wing Gly Val Val Leu 215 220 225

Leu Gly Ser Leu Phe Ser Arg Lys 230 Leu Gly Ser Leu Phe Ser Arg Lys 230

<210> 59 <210> 59

<211> 173 <211> 173

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 59 Met Gly Arg Gly Arg Cys Val Gly Pro Ser Leu Gln Leu Arg Gly 1 5 10 15 <400> 59 Met Gly Arg Gly Arg Cys Val Gly Pro Ser Leu Gln Leu Arg Gly 1 5 10 15

Gln Glu Trp Arg Cys Ser Pro Leu Val Pro Lys Gly Gly Ala Ala 20 25 30 Gln Glu Trp Arg Cys Ser Pro Leu Val Pro Lys Gly Gly Wing Wing 20 25 30

Ala Ala Glu Leu Gly Pro Gly Gly Gly Glu Asn Met Val Arg Arg 35 40 45 Wing Wing Glu Leu Gly Pro Gly Gly Gly Glu Asn Met Val Arg Arg 35 40 45

Phe Leu Val Thr Leu Arg Ile Arg Arg Ala Cys Gly Pro Pro Arg 50 55 60 Phe Leu Val Thr Leu Arg Ile Arg Arg Ala Cys Gly Pro Pro Arg 50 55 60

Val Arg Val Phe Val Val His Ile Pro Arg Leu Thr Gly Glu Trp 65 70 75 Val Arg Val Phe Val Val His Ile Pro Arg Leu Thr Gly Glu Trp 65 70 75

Ala Ala Pro Gly Ala Pro Ala Ala Val Ala Leu Val Leu Met Leu 80 85 90 Wing Pro Wing Gly Wing Pro Wing Val Wing Leu Val Leu Met Leu 80 85 90

Leu Arg Ser Gln Arg Leu Gly Gln Gln Pro Leu Pro Arg Arg Pro 95 100 105 Leu Arg Ser Gln Arg Leu Gly Gln Gln Pro Leu Pro Arg Arg Pro 95 100 105

Gly His Asp Asp Gly Gln Arg Pro Ser Gly Gly Ala Ala Ala Ala 110 115 120 Gly His Asp Asp Gly Gln Arg Pro Ser Gly Gly Wing Wing Wing 110 110 120

Pro Arg Arg Gly Ala Gln Leu Arg Arg Pro Arg His Ser His Pro 125 130 135 Pro Arg Arg Gly Ala Gln Leu Arg Arg Pro Arg His Ser His Pro 125 130 135

Thr Arg Ala Arg Arg Cys Pro Gly Gly Leu Pro Gly His Ala Gly 140 145 150 Thr Arg Ala Arg Arg Cys Pro Gly Gly Leu Pro Gly His Ala Gly 140 145 150

Gly Ala Ala Pro Gly Arg Gly Ala Ala Gly Arg Ala Arg Cys Leu 155 160 165 Gly Wing Wing Pro Gly Arg Gly Wing Wing Gly Arg Wing Arg Cys Leu 155 160 165

Gly Pro Ser Ala Arg Gly Pro Gly 170 Gly Pro Ser Wing Arg Gly Pro Gly 170

<210> 60 <210> 60

<211> 1342 <211> 1342

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 60 Met Arg Ala Asn Asp Ala Leu Gln Val Leu Gly Leu Leu Phe Ser 1 5 10 15 <400> 60 Met Arg Wing Asn Asp Wing Leu Gln Val Leu Gly Leu Leu Phe Ser 1 5 10 15

Leu Ala Arg Gly Ser Glu Val Gly Asn Ser Gln Ala Val Cys Pro 20 25 30 Leu Ala Arg Gly Ser Glu Val Gly Asn Ser Gln Ala Val Cys Pro 20 25 30

Gly Thr Leu Asn Gly Leu Ser Val Thr Gly Asp Ala Glu Asn Gln 35 40 45 Gly Thr Leu Asn Gly Leu Ser Val Thr Gly Asp Wing Glu Asn Gln 35 40 45

Tyr Gln Thr Leu Tyr Lys Leu Tyr Glu Arg Cys Glu Val Val Met 50 55 60 Tyr Gln Thr Leu Tyr Lys Leu Tyr Glu Arg Cys Glu Val Val Met 50 55 60

Gly Asn Leu Glu Ile Val Leu Thr Gly His Asn Ala Asp Leu Ser 65 70 75 Gly Asn Leu Glu Ile Val Leu Thr Gly His Asn Ala Asp Leu Ser 65 70 75

Phe Leu Gln Trp Ile Arg Glu Val Thr Gly Tyr Val Leu Val Ala 80 85 90 Phe Leu Gln Trp Ile Arg Glu Val Thr Gly Tyr Val Leu Val Wing 80 85 90

Met Asn Glu Phe Ser Thr Leu Pro Leu Pro Asn Leu Arg Val Val 95 100 105 Met Asn Glu Phe Ser Thr Leu Pro Leu Pro Asn Leu Arg Val Val 95 100 105

Arg Gly Thr Gln Val Tyr Asp Gly Lys Phe Ala Ile Phe Val Met 110 115 120 Arg Gly Thr Gln Val Tyr Asp Gly Lys Phe Wing Ile Phe Val Met 110 115 120

Leu Asn Tyr Asn Thr Asn Ser Ser His Ala Leu Arg Gln Leu Arg 125 130 135 Leu Asn Tyr Asn Thr Asn Be Being His Wing Leu Arg Gln Leu Arg 125 130 135

Leu Thr Gln Leu Thr Glu Ile Leu Ser Gly Gly Val Tyr Ile Glu 140 145 150 Leu Thr Gln Leu Thr Glu Ile Leu Ser Gly Gly Val Tyr Ile Glu 140 145 150

Lys Asn Asp Lys Leu Cys His Met Asp Thr Ile Asp Trp Arg Asp 155 160 165 Lys Asn Asp Lys Leu Cys His Met Asp Thr Ile Asp Trp Arg Asp 155 160 165

Ile Val Arg Asp Arg Asp Ala Glu Ile Val Val Lys Asp Asn Gly 170 175 180 Ile Val Arg Asp Arg Asp Wing Glu Ile Val Val Lys Asp Asn Gly 170 175 180

Arg Ser Cys Pro Pro Cys His Glu Val Cys Lys Gly Arg Cys Trp 185 190 195 Arg Ser Cys Pro Pro Cys His Glu Val Cys Lys Gly Arg Cys Trp 185 190 195

Gly Pro Gly Ser Glu Asp Cys Gln Thr Leu Thr Lys Thr Ile Cys 200 205 210 Gly Pro Gly Ser Glu Asp Cys Gln Thr Leu Thr Lys Thr Ile Cys 200 205 210

Ala Pro Gln Cys Asn Gly His Cys Phe Gly Pro Asn Pro Asn Gln 215 220 225 Wing Pro Gln Cys Asn Gly His Cys Phe Gly Pro Asn Pro Asn Gln 215 220 225

Cys Cys His Asp Glu Cys Ala Gly Gly Cys Ser Gly Pro Gln Asp 230 235 240 Cys Cys His Asp Glu Cys Wing Gly Gly Cys Ser Gly Pro Gln Asp 230 235 240

Thr Asp Cys Phe Ala Cys Arg His Phe Asn Asp Ser Gly Ala Cys 245 250 255 Thr Asp Cys Phe Ala Cys Arg His Phe Asn Asp Ser Gly Ala Cys 245 250 255

Val Pro Arg Cys Pro Gln Pro Leu Val Tyr Asn Lys Leu Thr Phe 260 265 270 Val Pro Arg Cys Pro Gln Pro Leu Val Tyr Asn Lys Leu Thr Phe 260 265 270

Gln Leu Glu Pro Asn Pro His Thr Lys Tyr Gln Tyr Gly Gly Val 275 280 285 Gln Leu Glu Pro Asn Pro His Thr Lys Tyr Gln Tyr Gly Gly Val 275 280 285

Cys Val Ala Ser Cys Pro His Asn Phe Val Val Asp Gln Thr Ser 290 295 300 Cys Val Arg Ala Cys Pro Pro Asp Lys Met Glu Val Asp Lys Asn 305 310 Cys Val Ala Ser Cys Pro His Asn Phe Val Val Asp Gln Thr Ser 290 295 300 Cys Val Arg Ala Cys Pro Pro Asp Lys Met Glu Val Asp Lys Asn 305 310

Gly Leu Lys Met Cys Glu Pro Cys Gly Gly Leu Cys Pro Lys Ala 320 325 330 Gly Leu Lys Met Cys Glu Pro Cys Gly Gly Leu Cys Pro Lys Wing 320 325 330

Cys Glu Gly Thr Gly Ser Gly Ser Arg Phe Gln Thr Val Asp Ser 335 340 345 Cys Glu Gly Thr Gly Ser Gly Ser Arg Phe Gln Thr Val Asp Ser 335 340 345

Ser Asn Ile Asp Gly Phe Val Asn Cys Thr Lys Ile Leu Gly Asn 350 355 360 Ser Asn Ile Asp Gly Phe Val Asn Cys Thr Lys Ile Leu Gly Asn 350 355 360

Leu Asp Phe Leu Ile Thr Gly Leu Asn Gly Asp Pro Trp His Lys 365 370 375 Leu Asp Phe Leu Ile Thr Gly Leu Asn Gly Asp Pro Trp His Lys 365 370 375

Ile Pro Ala Leu Asp Pro Glu Lys Leu Asn Val Phe Arg Thr Val 380 385 390 Ile Pro Wing Leu Asp Pro Glu Lys Leu Asn Val Phe Arg Thr Val 380 385 390

Arg Glu Ile Thr Gly Tyr Leu Asn Ile Gln Ser Trp Pro Pro His 395 400 405 Arg Glu Ile Thr Gly Tyr Leu Asn Ile Gln Ser Trp Pro Pro His 395 400 405

Met His Asn Phe Ser Val Phe Ser Asn Leu Thr Thr Ile Gly Gly 410 415 420 Met His Asn Phe Ser Val Phe Ser Asn Leu Thr Thr Ile Gly Gly 410 415 420

Arg Ser Leu Tyr Asn Arg Gly Phe Ser Leu Leu Ile Met Lys Asn 425 430 435 Arg Ser Leu Tyr Asn Arg Gly Phe Ser Leu Leu Ile Met Lys Asn 425 430 435

Leu Asn Val Thr Ser Leu Gly Phe Arg Ser Leu Lys Glu Ile Ser 440 445 450 Leu Asn Val Thr Ser Leu Gly Phe Arg Ser Leu Lys Glu Ile Ser 440 445 450

Ala Gly Arg Ile Tyr Ile Ser Ala Asn Arg Gln Leu Cys Tyr His 455 460 465 Ala Gly Arg Ile Tyr Ile Ser Ala Asn Arg Gln Leu Cys Tyr His 455 460 465

His Ser Leu Asn Trp Thr Lys Val Leu Arg Gly Pro Thr Glu Glu 470 475 480 His Ser Leu Asn Trp Thr Lys Val Leu Arg Gly Pro Thr Glu Glu 470 475 480

Arg Leu Asp Ile Lys His Asn Arg Pro Arg Arg Asp Cys Val Ala 485 490 495 Arg Leu Asp Ile Lys His Asn Arg Pro Arg Arg Asp Cys Val Ala 485 490 495

Glu Gly Lys Val Cys Asp Pro Leu Cys Ser Ser Gly Gly Cys Trp 500 505 510 Glu Gly Lys Val Cys Asp Pro Leu Cys Ser Ser Gly Gly Cys Trp 500 505 510

Gly Pro Gly Pro Gly Gln Cys Leu Ser Cys Arg Asn Tyr Ser Arg 515 520 525 Gly Pro Gly Pro Gly Gln Cys Leu Ser Cys Arg Asn Tyr Ser Arg 515 520 525

Gly Gly Val Cys Val Thr His Cys Asn Phe Leu Asn Gly Glu Pro 530 535 540 Gly Gly Val Cys Val Thr His Cys Asn Phe Leu Asn Gly Glu Pro 530 535 540

Arg Glu Phe Ala His Glu Ala Glu Cys Phe Ser Cys His Pro Glu 545 550 555 Arg Glu Phe Ala His Glu Ala Glu Cys Phe Ser Cys His Pro Glu 545 550 555

Cys Gln Pro Met Glu Gly Thr Ala Thr Cys Asn Gly Ser Gly Ser 560 565 570 Cys Gln Pro Met Glu Gly Thr Ala Thr Cys Asn Gly Ser Gly Ser 560 565 570

Asp Thr Cys Ala Gln Cys Ala His Phe Arg Asp Gly Pro His Cys 575 580 585 Asp Thr Cys Wing Gln Cys Wing His Phe Arg Asp Gly Pro His Cys 575 580 585

Val Ser Ser Cys Pro His Gly Val Leu Gly Ala Lys Gly Pro Ile 590 595 600 Val Ser Ser Cys Pro His Gly Val Leu Gly Ala Lys Gly Pro Ile 590 595 600

Tyr Lys Tyr Pro Asp Val Gln Asn Glu Cys Arg Pro Cys His Glu 605 610 615 Tyr Lys Tyr Pro Asp Val Gln Asn Glu Cys Arg Pro Cys His Glu 605 610 615

Asn Cys Thr Gln Gly Cys Lys Gly Pro Glu Leu Gln Asp Cys Leu 620 625 630 Asn Cys Thr Gln Gly Cys Lys Gly Pro Glu Leu Gln Asp Cys Leu 620 625 630

Gly Gln Thr Leu Val Leu Ile Gly Lys Thr His Leu Thr Met Ala Gly Gln Thr Leu Val Leu Ile Gly Lys Thr His Leu Thr Met Ala

635 640 635 640

Leu Thr Val Ile Ala Gly Leu Val Val Ile Phe Met Met Leu Gly 650 655 660 Leu Thr Val Ile Wing Gly Leu Val Val Ile Phe Met Met Leu Gly 650 655 660

Gly Thr Phe Leu Tyr Trp Arg Gly Arg Arg Ile Gln Asn Lys Arg 665 670 675 Gly Thr Phe Leu Tyr Trp Arg Gly Arg Arg Ile Gln Asn Lys Arg 665 670 675

Ala Met Arg Arg Tyr Leu Glu Arg Gly Glu Ser Ile Glu Pro Leu 680 685 690 Wing Met Arg Arg Tyr Leu Glu Arg Gly Glu Ser Ile Glu Pro Leu 680 685 690

Asp Pro Ser Glu Lys Ala Asn Lys Val Leu Ala Arg Ile Phe Lys 695 700 705 Asp Pro Ser Glu Lys Wing Asn Lys Val Leu Wing Arg Ile Phe Lys 695 700 705

Glu Thr Glu Leu Arg Lys Leu Lys Val Leu Gly Ser Gly Val Phe 710 715 720 Glu Thr Glu Leu Arg Lys Leu Lys Val Leu Gly Ser Gly Val Phe 710 715 720

Gly Thr Val His Lys Gly Val Trp Ile Pro Glu Gly Glu Ser Ile 725 730 735 Gly Thr Val His Lys Gly Val Trp Ile Pro Glu Gly Glu Ser Ile 725 730 735

Lys Ile Pro Val Cys Ile Lys Val Ile Glu Asp Lys Ser Gly Arg 740 745 750 Lys Ile Pro Val Cys Ile Lys Val Ile Glu Asp Lys Ser Gly Arg 740 745 750

Gln Ser Phe Gln Ala Val Thr Asp His Met Leu Ala Ile Gly Ser 755 760 765 Gln Ser Phe Gln Ala Val Thr Asp His Met Leu Ile Wing Gly Ser 755 760 765

Leu Asp His Ala His Ile Val Arg Leu Leu Gly Leu Cys Pro Gly 770 775 780 Leu Asp His Wing His Ile Val Arg Leu Leu Gly Leu Cys Pro Gly 770 775 780

Ser Ser Leu Gln Leu Val Thr Gln Tyr Leu Pro Leu Gly Ser Leu 785 790 795 Be Ser Leu Gln Leu Val Thr Gln Tyr Leu Pro Leu Gly Ser Leu 785 790 795

Leu Asp His Val Arg Gln His Arg Gly Ala Leu Gly Pro Gln Leu 800 805 810 Leu Asp His Val Arg Gln His Arg Gly Ala Leu Gly Pro Gln Leu 800 805 810

Leu Leu Asn Trp Gly Val Gln Ile Ala Lys Gly Met Tyr Tyr Leu 815 820 825 Leu Leu Asn Trp Gly Val Gln Ile Wing Lys Gly Met Tyr Tyr Leu 815 820 825

Glu Glu His Gly Met Val His Arg Asn Leu Ala Ala Arg Asn Val 830 835 840 Glu Glu His Gly Met Val His Arg Asn Leu Ala Wing Arg Asn Val 830 835 840

Leu Leu Lys Ser Pro Ser Gln Val Gln Val Ala Asp Phe Gly Val 845 850 855 Leu Leu Lys Ser Pro Ser Gln Val Gln Val Wing Asp Phe Gly Val 845 850 855

Ala Asp Leu Leu Pro Pro Asp Asp Lys Gln Leu Leu Tyr Ser Glu 860 865 870 Wing Asp Leu Leu Pro Pro Asp Asp Lys Gln Leu Leu Tyr Ser Glu 860 865 870

Ala Lys Thr Pro Ile Lys Trp Met Ala Leu Glu Ser Ile His Phe 875 880 885 Wing Lys Thr Pro Ile Lys Trp Met Wing Leu Glu Ser Ile His Phe 875 880 885

Gly Lys Tyr Thr His Gln Ser Asp Val Trp Ser Tyr Gly Val Thr 890 895 900 Gly Lys Tyr Thr His Gln Ser Asp Val Trp Ser Tyr Gly Val Thr 890 895 900

Val Trp Glu Leu Met Thr Phe Gly Ala Glu Pro Tyr Ala Gly Leu 905 910 915 Val Trp Glu Leu Met Thr Phe Gly Ala Glu Pro Tyr Ala Gly Leu 905 910 915

Arg Leu Ala Glu Val Pro Asp Leu Leu Glu Lys Gly Glu Arg Leu 920 925 930 Arg Leu Wing Glu Val Pro Asp Leu Leu Glu Lys Gly Glu Arg Leu 920 925 930

Ala Gln Pro Gln Ile Cys Thr Ile Asp Val Tyr Met Val Met Val 935 940 945 Wing Gln Pro Gln Ile Cys Thr Ile Asp Val Tyr Met Val Met Val 935 940 945

Lys Cys Trp Met Ile Asp Glu Asn Ile Arg Pro Thr Phe Lys Glu 950 955 960 Lys Cys Trp Met Ile Asp Glu Asn Ile Arg Pro Thr Phe Lys Glu 950 955 960

Leu Ala Asn Glu Phe Thr Arg Met Ala Arg Asp Pro Pro Arg Tyr 965 970 Leu Wing Asn Glu Phe Thr Arg Met Wing Arg Asp Pro Pro Arg Tyr 965 970

Leu Val Ile Lys Arg Glu Ser Gly Pro Gly Ile Ala Pro Gly Pro 980 985 Leu Val Ile Lys Arg Glu Ser Gly Pro Gly Ile Ala Pro Gly Pro 980 985

Glu Pro His Gly Leu Thr Asn Lys Lys Leu Glu Glu Val Glu Leu 995 1000 1005 Glu Pro His Gly Leu Thr Asn Lys Lys Leu Glu Glu Val Glu Leu 995 1000 1005

Glu Pro Glu Leu Asp Leu Asp Leu Asp Leu Glu Ala Glu Glu Asp 1010 1015 1020 Glu Pro Glu Leu Asp Leu Asp Leu Asp Leu Glu Ala Glu Glu Asp 1010 1015 1020

Asn Leu Ala Thr Thr Thr Leu Gly Ser Ala Leu Ser Leu Pro Val 1025 1030 1035 Asn Leu Ala Thr Thr Thr Leu Gly Ser Ala Leu Ser Leu Pro Val 1025 1030 1035

Gly Thr Leu Asn Arg Pro Arg Gly Ser Gln Ser Leu Leu Ser Pro 1040 1045 1050 Gly Thr Leu Asn Arg Pro Arg Gly Ser Gln Ser Leu Leu Ser Pro 1040 1045 1050

Ser Ser Gly Tyr Met Pro Met Asn Gln Gly Asn Leu Gly Glu Ser 1055 1060 1065 Be Ser Gly Tyr Met Pro Met Asn Gln Gly Asn Leu Gly Glu Ser 1055 1060 1065

Cys Gln Glu Ser Ala Val Ser Gly Ser Ser Glu Arg Cys Pro Arg 1070 1075 1080 Cys Gln Glu Ser Ala Val Ser Gly Ser Ser Glu Arg Cys Pro Arg 1070 1075 1080

Pro Val Ser Leu His Pro Met Pro Arg Gly Cys Leu Ala Ser Glu 1085 1090 1095 Pro Val Ser Leu His Pro Met Pro Arg Gly Cys Leu Ala Ser Glu 1085 1090 1095

Ser Ser Glu Gly His Val Thr Gly Ser Glu Ala Glu Leu Gln Glu 1100 1105 1110 Ser Ser Glu Gly His Val Thr Gly Ser Glu Ala Glu Leu Gln Glu 1100 1105 1110

Lys Val Ser Met Cys Arg Ser Arg Ser Arg Ser Arg Ser Pro Arg 1115 1120 1125 Lys Val Ser Met Cys Arg Ser Arg Ser Arg Ser Arg Ser Pro Arg 1115 1120 1125

Pro Arg Gly Asp Ser Ala Tyr His Ser Gln Arg His Ser Leu Leu 1130 1135 1140 Pro Arg Gly Asp Ser Ala Tyr His Ser Gln Arg His Ser Leu Leu 1130 1135 1140

Thr Pro Val Thr Pro Leu Ser Pro Pro Gly Leu Glu Glu Glu Asp 1145 1150 1155 Thr Pro Val Thr Pro Leu Ser Pro Pro Gly Leu Glu Glu Glu Asp 1145 1150 1155

Val Asn Gly Tyr Val Met Pro Asp Thr His Leu Lys Gly Thr Pro 1160 1165 1170 Val Asn Gly Tyr Val Met Pro Asp Thr His Leu Lys Gly Thr Pro 1160 1165 1170

Ser Ser Arg Glu Gly Thr Leu Ser Ser Val Gly Leu Ser Ser Val 1175 1180 1185 Be Be Arg Glu Gly Thr Leu Be Be Val Gly Leu Be Be Val 1175 1180 1185

Leu Gly Thr Glu Glu Glu Asp Glu Asp Glu Glu Tyr Glu Tyr Met 1190 1195 1200 Leu Gly Thr Glu Glu Glu Asp Glu Asp Glu Glu Tyr Glu Tyr Met 1190 1195 1200

Asn Arg Arg Arg Arg His Ser Pro Pro His Pro Pro Arg Pro Ser 1205 1210 1215 Asn Arg Arg Arg Arg His Ser Pro Pro His Pro Pro Arg Pro Ser 1205 1210 1215

Ser Leu Glu Glu Leu Gly Tyr Glu Tyr Met Asp Val Gly Ser Asp 1220 1225 1230 Ser Leu Glu Glu Leu Gly Tyr Glu Tyr Met Asp Val Gly Ser Asp 1220 1225 1230

Leu Ser Ala Ser Leu Gly Ser Thr Gln Ser Cys Pro Leu His Pro 1235 1240 1245 Leu Ser Ala Ser Leu Gly Ser Thr Gln Ser Cys Pro Leu His Pro 1235 1240 1245

Val Pro Ile Met Pro Thr Ala Gly Thr Thr Pro Asp Glu Asp Tyr 1250 1255 1260 Val Pro Ile Met Pro Thr Wing Gly Thr Thr Pro Asp Glu Asp Tyr 1250 1255 1260

Glu Tyr Met Asn Arg Gln Arg Asp Gly Gly Gly Pro Gly Gly Asp 1265 1270 1275 Glu Tyr Met Asn Arg Gln Arg Asp Gly Gly Gly Pro Gly Gly Asp 1265 1270 1275

Tyr Ala Ala Met Gly Ala Cys Pro Ala Ser Glu Gln Gly Tyr Glu 1280 1285 1290 Tyr Ala Wing Met Gly Ala Cys Pro Ala Ser Glu Gln Gly Tyr Glu 1280 1285 1290

Glu Met Arg Ala Phe Gln Gly Pro Gly His Gln Ala Pro His Val 1295 1300 1305 Glu Met Arg Ala Phe Gln Gly Pro Gly His Gln Ala Pro His Val 1295 1300 1305

His Tyr Ala Arg Leu Lys Thr Leu Arg Ser Leu Glu Ala Thr Asp 1310 1315 1320 Ser Ala Phe Asp Asn Pro Asp Tyr Trp His Ser Arg Leu Phe Pro 1325 1330 1335 His Tyr Ala Arg Leu Lys Thr Leu Arg Ser Leu Glu Ala Thr Asp 1310 1315 1320 Ser Ala Phe Asp Asn Pro Asp Tyr Trp His Ser Arg Leu Phe Pro 1325 1330 1335

Lys Ala Asn Ala Gln Arg Thr 1340 Lys Wing Asn Wing Gln Arg Thr 1340

<210> 61 <210> 61

<211> 1308 <211> 1308

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 61 Met Lys Pro Ala Thr Gly Leu Trp Val Trp Val Ser Leu Leu Val 1 5 10 15 <400> 61 Met Lys Pro Wing Thr Gly Leu Trp Val Trp Val Ser Leu Leu Val 1 5 10 15

Ala Ala Gly Thr Val Gln Pro Ser Asp Ser Gln Ser Val Cys Ala 20 25 30 Wing Wing Gly Thr Val Gln Pro Ser Asp Ser Gln Ser Val Cys Wing 20 25 30

Gly Thr Glu Asn Lys Leu Ser Ser Leu Ser Asp Leu Glu Gln Gln 35 40 45 Gly Thr Glu Asn Lys Leu Be Be Leu Be Asp Leu Glu Gln Gln 35 40 45

Tyr Arg Ala Leu Arg Lys Tyr Tyr Glu Asn Cys Glu Val Val Met 50 55 60 Tyr Arg Ala Leu Arg Lys Tyr Tyr Glu Asn Cys Glu Val Val Met 50 55 60

Gly Asn Leu Glu Ile Thr Ser Ile Glu His Asn Arg Asp Leu Ser 65 70 75 Gly Asn Leu Glu Ile Thr Ser Ile Glu His Asn Arg Asp Leu Ser 65 70 75

Phe Leu Arg Ser Val Arg Glu Val Thr Gly Tyr Val Leu Val Ala 80 85 90 Phe Leu Arg Ser Val Arg Glu Val Thr Gly Tyr Val Leu Val Wing 80 85 90

Leu Asn Gln Phe Arg Tyr Leu Pro Leu Glu Asn Leu Arg Ile Ile 95 100 105 Leu Asn Gln Phe Arg Tyr Leu Pro Leu Glu Asn Leu Arg Ile Ile 95 100 105

Arg Gly Thr Lys Leu Tyr Glu Asp Arg Tyr Ala Leu Ala Ile Phe 110 115 120 Arg Gly Thr Lys Leu Tyr Glu Asp Arg Tyr Ala Leu Ile Phe 110 115 120

Leu Asn Tyr Arg Lys Asp Gly Asn Phe Gly Leu Gln Glu Leu Gly 125 130 135 Leu Asn Tyr Arg Lys Asp Gly Asn Phe Gly Leu Gln Glu Leu Gly 125 130 135

Leu Lys Asn Leu Thr Glu Ile Leu Asn Gly Gly Val Tyr Val Asp 140 145 150 Leu Lys Asn Leu Thr Glu Ile Leu Asn Gly Gly Val Tyr Val Asp 140 145 150

Gln Asn Lys Phe Leu Cys Tyr Ala Asp Thr Ile His Trp Gln Asp 155 160 165 Gln Asn Lys Phe Leu Cys Tyr Ala Asp Thr Ile His Trp Gln Asp 155 160 165

Ile Val Arg Asn Pro Trp Pro Ser Asn Leu Thr Leu Val Ser Thr 170 175 180 Ile Val Arg Asn Pro Trp Pro Ser Asn Leu Thr Leu Val Ser Thr 170 175 180

Asn Gly Ser Ser Gly Cys Gly Arg Cys His Lys Ser Cys Thr Gly 185 190 195 Asn Gly Ser Ser Gly Cys Gly Arg Cys His Lys Ser Cys Thr Gly 185 190 195

Arg Cys Trp Gly Pro Thr Glu Asn His Cys Gln Thr Leu Thr Arg 200 205 210 Arg Cys Trp Gly Pro Thr Glu Asn His Cys Gln Thr Leu Thr Arg 200 205 210

Thr Val Cys Ala Glu Gln Cys Asp Gly Arg Cys Tyr Gly Pro Tyr 215 220 225 Thr Val Cys Wing Glu Gln Cys Asp Gly Arg Cys Tyr Gly Pro Tyr 215 220 225

Val Ser Asp Cys Cys His Arg Glu Cys Ala Gly Gly Cys Ser Gly 230 235 240 Val Ser Asp Cys Cys His Arg Glu Cys Wing Gly Gly Cys Ser Gly 230 235 240

Pro Lys Asp Thr Asp Cys Phe Ala Cys Met Asn Phe Asn Asp Ser 245 250 255 Pro Lys Asp Thr Asp Cys Phe Ala Cys Met Asn Phe Asn Asp Ser 245 250 255

Gly Ala Cys Val Thr Gln Cys Pro Gln Thr Phe Val Tyr Asn Pro 260 265 270 Gly Ala Cys Val Thr Gln Cys Pro Gln Thr Phe Val Tyr Asn Pro 260 265 270

Thr Thr Phe Gln Leu Glu His Asn Phe Asn Ala Lys Tyr Thr Tyr Thr Thr Phe Gln Leu Glu His Asn Phe Asn Ala Lys Tyr Thr Tyr

275 280 275 280

Gly Ala Phe Cys Val Lys Lys Cys Pro His Asn Phe Val Val Asp 290 295 300 Gly Ala Phe Cys Val Lys Lys Cys Pro His Asn Phe Val Val Asp 290 295 300

Ser Ser Ser Cys Val Arg Ala Cys Pro Ser Ser Lys Met Glu Val 305 310 315 Be Be Be Cys Val Arg Wing Cys Pro Be Be Lys Met Glu Val 305 310 315

Glu Glu Asn Gly Ile Lys Met Cys Lys Pro Cys Thr Asp Ile Cys 320 325 330 Glu Glu Asn Gly Ile Lys Met Cys Lys Pro Cys Thr Asp Ile Cys 320 325 330

Pro Lys Ala Cys Asp Gly Ile Gly Thr Gly Ser Leu Met Ser Ala 335 340 345 Pro Lys Ala Cys Asp Gly Ile Gly Thr Gly Ser Leu Met Ser Ala 335 340 345

Gln Thr Val Asp Ser Ser Asn Ile Asp Lys Phe Ile Asn Cys Thr 350 355 360 Gln Thr Val Asp Ser Ser Asn Ile Asp Lys Phe Ile Asn Cys Thr 350 355 360

Lys Ile Asn Gly Asn Leu Ile Phe Leu Val Thr Gly Ile His Gly 365 370 375 Lys Ile Asn Gly Asn Leu Ile Phe Leu Val Thr Gly Ile His Gly 365 370 375

Asp Pro Tyr Asn Ala Ile Glu Ala Ile Asp Pro Glu Lys Leu Asn 380 385 390 Asp Pro Tyr Asn Ile Wing Glu Ile Wing Asp Pro Glu Lys Leu Asn 380 385 390

Val Phe Arg Thr Val Arg Glu Ile Thr Gly Phe Leu Asn Ile Gln 395 400 405 Val Phe Arg Thr Val Arg Glu Ile Thr Gly Phe Leu Asn Ile Gln 395 400 405

Ser Trp Pro Pro Asn Met Thr Asp Phe Ser Val Phe Ser Asn Leu 410 415 420 Ser Trp Pro Pro Asn Met Thr Asp Phe Ser Val Phe Ser Asn Leu 410 415 420

Val Thr Ile Gly Gly Arg Val Leu Tyr Ser Gly Leu Ser Leu Leu 425 430 435 Val Thr Ile Gly Gly Arg Val Leu Tyr Ser Gly Leu Ser Leu Leu 425 430 435

Ile Leu Lys Gln Gln Gly Ile Thr Ser Leu Gln Phe Gln Ser Leu 440 445 450 Ile Leu Lys Gln Gln Gly Ile Thr Ser Leu Gln Phe Gln Ser Leu 440 445 450

Lys Glu Ile Ser Ala Gly Asn Ile Tyr Ile Thr Asp Asn Ser Asn 455 460 465 Lys Glu Ile Ser Ala Gly Asn Ile Tyr Ile Thr Asp Asn Ser Asn 455 460 465

Leu Cys Tyr Tyr His Thr Ile Asn Trp Thr Thr Leu Phe Ser Thr 470 475 480 Leu Cys Tyr Tyr His Thr Ile Asn Trp Thr Thr Leu Phe Ser Thr 470 475 480

Ile Asn Gln Arg Ile Val Ile Arg Asp Asn Arg Lys Ala Glu Asn 485 490 495 Ile Asn Gln Arg Ile Val Ile Arg Asp Asn Arg Lys Ala Glu Asn 485 490 495

Cys Thr Ala Glu Gly Met Val Cys Asn His Leu Cys Ser Ser Asp 500 505 510 Cys Thr Wing Glu Gly Met Val Cys Asn His Leu Cys Ser Ser Asp 500 505 510

Gly Cys Trp Gly Pro Gly Pro Asp Gln Cys Leu Ser Cys Arg Arg 515 520 525 Gly Cys Trp Gly Pro Gly Pro Asp Gln Cys Leu Ser Cys Arg Arg 515 520 525

Phe Ser Arg Gly Arg Ile Cys Ile Glu Ser Cys Asn Leu Tyr Asp 530 535 540 Phe Ser Arg Gly Arg Ile Cys Ile Glu Ser Cys Asn Leu Tyr Asp 530 535 540

Gly Glu Phe Arg Glu Phe Glu Asn Gly Ser Ile Cys Val Glu Cys 545 550 555 Gly Glu Phe Arg Glu Phe Glu Asn Gly Ser Ile Cys Val Glu Cys 545 550 555

Asp Pro Gln Cys Glu Lys Met Glu Asp Gly Leu Leu Thr Cys His 560 565 570 Asp Pro Gln Cys Glu Lys Met Glu Asp Gly Leu Leu Thr Cys His 560 565 570

Gly Pro Gly Pro Asp Asn Cys Thr Lys Cys Ser His Phe Lys Asp 575 580 585 Gly Pro Gly Pro Asp Asn Cys Thr Lys Cys Ser His Phe Lys Asp 575 580 585

Gly Pro Asn Cys Val Glu Lys Cys Pro Asp Gly Leu Gln Gly Ala 590 595 600 Gly Pro Asn Cys Val Glu Lys Cys Pro Asp Gly Leu Gln Gly Ala 590 595 600

Asn Ser Phe Ile Phe Lys Tyr Ala Asp Pro Asp Arg Glu Cys His 605 610 Asn Ser Phe Ile Phe Lys Tyr Ala Asp Pro Asp Arg Glu Cys His 605 610

Pro Cys His Pro Asn Cys Thr Gln Gly Cys Asn Gly Pro Thr Ser 620 625 Pro Cys His Pro Asn Cys Thr Gln Gly Cys Asn Gly Pro Thr Ser 620 625

His Asp Cys Ile Tyr Tyr Pro Trp Thr Gly His Ser Thr Leu Pro 635 640 645 His Asp Cys Ile Tyr Tyr Pro Trp Thr Gly His Ser Thr Leu Pro 635 640 645

Gln His Ala Arg Thr Pro Leu Ile Ala Ala Gly Val Ile Gly Gly 650 655 660 Gln His Wing Arg Thr Pro Leu Ile Wing Wing Gly Val Ile Gly Gly 650 655 660

Leu Phe Ile Leu Val Ile Val Gly Leu Thr Phe Ala Val Tyr Val 665 670 675 Leu Phe Ile Leu Val Ile Val Gly Leu Thr Phe Ala Val Tyr Val 665 670 675

Arg Arg Lys Ser Ile Lys Lys Lys Arg Ala Leu Arg Arg Phe Leu 680 685 690 Arg Arg Lys Ser Ile Lys Lys Lys Arg Ala Leu Arg Arg Phe Leu 680 685 690

Glu Thr Glu Leu Val Glu Pro Leu Thr Pro Ser Gly Thr Ala Pro 695 700 705 Glu Thr Glu Leu Val Glu Pro Leu Thr Pro Ser Gly Thr Ala Pro 695 700 705

Asn Gln Ala Gln Leu Arg Ile Leu Lys Glu Thr Glu Leu Lys Arg 710 715 720 Asn Gln Wing Gln Leu Arg Ile Leu Lys Glu Thr Glu Leu Lys Arg 710 715 720

Val Lys Val Leu Gly Ser Gly Ala Phe Gly Thr Val Tyr Lys Gly 725 730 735 Val Lys Val Leu Gly Ser Gly Ala Phe Gly Thr Val Tyr Lys Gly 725 730 735

Ile Trp Val Pro Glu Gly Glu Thr Val Lys Ile Pro Val Ala Ile 740 745 750 Ile Trp Val Pro Glu Gly Glu Thr Val Lys Ile Pro Val Wing 740 745 750

Lys Ile Leu Asn Glu Thr Thr Gly Pro Lys Ala Asn Val Glu Phe 755 760 765 Lys Ile Leu Asn Glu Thr Thr Gly Pro Lys Wing Asn Val Glu Phe 755 760 765

Met Asp Glu Ala Leu Ile Met Ala Ser Met Asp His Pro His Leu 770 775 780 Met Asp Glu Ala Leu Ile Met Ala Ser Met Asp His Pro His Leu 770 775 780

Val Arg Leu Leu Gly Val Cys Leu Ser Pro Thr Ile Gln Leu Val 785 790 795 Val Arg Leu Leu Gly Val Cys Leu Ser Pro Thr Ile Gln Leu Val 785 790 795

Thr Gln Leu Met Pro His Gly Cys Leu Leu Glu Tyr Val His Glu 800 805 810 Thr Gln Leu Met Pro His Gly Cys Leu Leu Glu Tyr Val His Glu 800 805 810

His Lys Asp Asn Ile Gly Ser Gln Leu Leu Leu Asn Trp Cys Val 815 820 825 His Lys Asp Asn Ile Gly Ser Gln Leu Leu Leu Asn Trp Cys Val 815 820 825

Gln Ile Ala Lys Gly Met Met Tyr Leu Glu Glu Arg Arg Leu Val 830 835 840 Gln Ile Ala Lys Gly Met Met Tyr Leu Glu Glu Arg Arg Leu Val 830 835 840

His Arg Asp Leu Ala Ala Arg Asn Val Leu Val Lys Ser Pro Asn 845 850 855 His Arg Asp Leu Ala Wing Arg Asn Val Leu Val Lys Ser Pro Asn 845 850 855

His Val Lys Ile Thr Asp Phe Gly Leu Ala Arg Leu Leu Glu Gly 860 865 870 His Val Lys Ile Thr Asp Phe Gly Leu Wing Arg Leu Leu Glu Gly 860 865 870

Asp Glu Lys Glu Tyr Asn Ala Asp Gly Gly Lys Met Pro Ile Lys 875 880 885 Asp Glu Lys Glu Tyr Asn Wing Asp Gly Gly Lys Met Pro Ile Lys 875 880 885

Trp Met Ala Leu Glu Cys Ile His Tyr Arg Lys Phe Thr His Gln 890 895 900 Trp Met Wing Leu Glu Cys Ile His Tyr Arg Lys Phe Thr His Gln 890 895 900

Ser Asp Val Trp Ser Tyr Gly Val Thr Ile Trp Glu Leu Met Thr 905 910 915 Ser Asp Val Trp Ser Tyr Gly Val Thr Ile Trp Glu Leu Met Thr 905 910 915

Phe Gly Gly Lys Pro Tyr Asp Gly Ile Pro Thr Arg Glu Ile Pro 920 925 930 Phe Gly Gly Lys Pro Tyr Asp Gly Ile Pro Thr Arg Glu Ile Pro 920 925 930

Asp Leu Leu Glu Lys Gly Glu Arg Leu Pro Gln Pro Pro Ile Cys 935 940 945 Asp Leu Leu Glu Lys Gly Glu Arg Leu Pro Gln Pro Pro Ile Cys 935 940 945

Thr Ile Asp Val Tyr Met Val Met Val Lys Cys Trp Met Ile Asp 950 955 Thr Ile Asp Val Tyr Met Val Met Val Lys Cys Trp Met Ile Asp 950 955

Ala Asp Ser Arg Pro Lys Phe Lys Glu Leu Ala Ala Glu Phe Ser 965 970 Wing Asp Ser Arg Pro Lys Phe Lys Glu Leu Wing Glu Phe Ser 965 970

Arg Met Ala Arg Asp Pro Gln Arg Tyr Leu Val Ile Gln Gly Asp 980 985 Arg Met Wing Arg Asp Pro Gln Arg Tyr Leu Val Ile Gln Gly Asp 980 985

Asp Arg Met Lys Leu Pro Ser Pro Asn Asp Ser Lys Phe Phe Gln 995 1000 1005 Asp Arg Met Lys Leu Pro Ser Pro Asn Asp Ser Lys Phe Phe Gln 995 1000 1005

Asn Leu Leu Asp Glu Glu Asp Leu Glu Asp Met Met Asp Ala Glu 1010 1015 1020 Asn Leu Leu Asp Glu Glu Asp Leu Glu Asp Met Met Asp Ala Glu 1010 1015 1020

Glu Tyr Leu Val Pro Gln Ala Phe Asn Ile Pro Pro Pro Ile Tyr 1025 1030 1035 Glu Tyr Leu Val Pro Gln Wing Phe Asn Ile Pro Pro Pro Ile Tyr 1025 1030 1035

Thr Ser Arg Ala Arg Ile Asp Ser Asn Arg Ser Glu Ile Gly His 1040 1045 1050 Thr Ser Arg Ala Arg Ile Asp Ser Asn Arg Ser Glu Ile Gly His 1040 1045 1050

Ser Pro Pro Pro Ala Tyr Thr Pro Met Ser Gly Asn Gln Phe Val 1055 1060 1065 Ser Pro Pro Pro Wing Tyr Thr Pro Met Ser Gly Asn Gln Phe Val 1055 1060 1065

Tyr Arg Asp Gly Gly Phe Ala Ala Glu Gln Gly Val Ser Val Pro 1070 1075 1080 Tyr Arg Asp Gly Gly Phe Wing Wing Glu Gln Gly Val Ser Val Pro 1070 1075 1080

Tyr Arg Ala Pro Thr Ser Thr Ile Pro Glu Ala Pro Val Ala Gln 1085 1090 1095 Tyr Arg Pro Wing Thr Ser Thr Ile Pro Glu Wing Pro Val Wing Gln 1085 1090 1095

Gly Ala Thr Ala Glu Ile Phe Asp Asp Ser Cys Cys Asn Gly Thr 1100 1105 1110 Gly Wing Thr Wing Glu Ile Phe Asp Asp Ser Cys Cys Asn Gly Thr 1100 1105 1110

Leu Arg Lys Pro Val Ala Pro His Val Gln Glu Asp Ser Ser Thr 1115 1120 1125 Leu Arg Lys Pro Val Ala Pro His Val Gln Glu Asp Ser Ser Thr 1115 1120 1125

Gln Arg Tyr Ser Ala Asp Pro Thr Val Phe Ala Pro Glu Arg Ser 1130 1135 1140 Gln Arg Tyr Ser Wing Asp Pro Thr Val Phe Wing Pro Glu Arg Ser 1130 1135 1140

Pro Arg Gly Glu Leu Asp Glu Glu Gly Tyr Met Thr Pro Met Arg 1145 1150 1155 Pro Arg Gly Glu Leu Asp Glu Glu Gly Tyr Met Thr Pro Met Arg 1145 1150 1155

Asp Lys Pro Lys Gln Glu Tyr Leu Asn Pro Val Glu Glu Asn Pro 1160 1165 1170 Asp Lys Pro Lys Gln Glu Tyr Leu Asn Pro Val Glu Glu Asn Pro 1160 1165 1170

Phe Val Ser Arg Arg Lys Asn Gly Asp Leu Gln Ala Leu Asp Asn 1175 1180 1185 Phe Val Ser Arg Arg Lys Asn Gly Asp Leu Gln Ala Leu Asp Asn 1175 1180 1185

Pro Glu Tyr His Asn Ala Ser Asn Gly Pro Pro Lys Ala Glu Asp 1190 1195 1200 Pro Glu Tyr His Asn Ala Ser Asn Gly Pro Pro Lys Ala Glu Asp 1190 1195 1200

Glu Tyr Val Asn Glu Pro Leu Tyr Leu Asn Thr Phe Ala Asn Thr 1205 1210 1215 Glu Tyr Val Asn Glu Pro Leu Tyr Leu Asn Thr Phe Ala Asn Thr 1205 1210 1215

Leu Gly Lys Ala Glu Tyr Leu Lys Asn Asn Ile Leu Ser Met Pro 1220 1225 1230 Leu Gly Lys Wing Glu Tyr Leu Lys Asn Asn Ile Leu Ser Met Pro 1220 1225 1230

Glu Lys Ala Lys Lys Ala Phe Asp Asn Pro Asp Tyr Trp Asn His 1235 1240 1245 Glu Lys Wing Lys Lys Wing Phe Asp Asn Pro Asp Tyr Trp Asn His 1235 1240 1245

Ser Leu Pro Pro Arg Ser Thr Leu Gln His Pro Asp Tyr Leu Gln 1250 1255 1260 Ser Leu Pro Pro Arg Ser Thr Leu Gln His Pro Asp Tyr Leu Gln 1250 1255 1260

Glu Tyr Ser Thr Lys Tyr Phe Tyr Lys Gln Asn Gly Arg Ile Arg 1265 1270 1275 Glu Tyr Ser Thr Lys Tyr Phe Tyr Lys Gln Asn Gly Arg Ile Arg 1265 1270 1275

Pro Ile Val Ala Glu Asn Pro Glu Tyr Leu Ser Glu Phe Ser Leu 1280 1285 1290 Pro Ile Val Wing Glu Asn Pro Glu Tyr Leu Ser Glu Phe Ser Leu 1280 1285 1290

Lys Pro Gly Thr Val Leu Pro Pro Pro Pro Tyr Arg His Arg Asn Lys Pro Gly Thr Val Leu Pro Pro Pro Pro Tyr Arg His Arg Asn

1295 1300 1305 1295 1300 1305

Thr Val Val Thr Val Val

<210> 62 <210> 62

<211> 806 <211> 806

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 62 Met Gly Ala Pro Ala Cys Ala Leu Ala Leu Cys Val Ala Val Ala 1 5 10 15 <400> 62 Met Gly Pro Wing Cys Wing Leu Wing Leu Cys Val Wing Val Wing 1 5 10 15

Ile Val Ala Gly Ala Ser Ser Glu Ser Leu Gly Thr Glu Gln Arg 20 25 30 Ile Val Ala Gly Ala Ser Ser Glu Ser Leu Gly Thr Glu Gln Arg 20 25 30

Val Val Gly Arg Ala Ala Glu Val Pro Gly Pro Glu Pro Gly Gln 35 40 45 Val Val Gly Arg Wing Glu Glu Pro Pro Gly Pro Glu Pro Gly Gln 35 40 45

Gln Glu Gln Leu Val Phe Gly Ser Gly Asp Ala Val Glu Leu Ser 50 55 60 Gln Glu Gln Leu Val Phe Gly Ser Gly Asp Ala Val Glu Leu Ser 50 55 60

Cys Pro Pro Pro Gly Gly Gly Pro Met Gly Pro Thr Val Trp Val 65 70 75 Cys Pro Pro Pro Gly Gly Gly Pro Met Gly Pro Thr Val Trp Val 65 70 75

Lys Asp Gly Thr Gly Leu Val Pro Ser Glu Arg Val Leu Val Gly 80 85 90 Lys Asp Gly Thr Gly Leu Val Pro Ser Glu Arg Val Leu Val Gly 80 85 90

Pro Gln Arg Leu Gln Val Leu Asn Ala Ser His Glu Asp Ser Gly 95 100 105 Pro Gln Arg Leu Gln Val Leu Asn Ala Ser His Glu Asp Ser Gly 95 100 105

Ala Tyr Ser Cys Arg Gln Arg Leu Thr Gln Arg Val Leu Cys His 110 115 120 Wing Tyr Ser Cys Arg Gln Arg Leu Thr Gln Arg Val Leu Cys His 110 115 120

Phe Ser Val Arg Val Thr Asp Ala Pro Ser Ser Gly Asp Asp Glu 125 130 135 Phe Ser Val Arg Val Thr Asp Wing Pro Be Ser Gly Asp Asp Glu 125 130 135

Asp Gly Glu Asp Glu Ala Glu Asp Thr Gly Val Asp Thr Gly Ala 140 145 150 Asp Gly Glu Asp Glu Ala Glu Asp Thr Gly Val Asp Thr Gly Ala 140 145 150

Pro Tyr Trp Thr Arg Pro Glu Arg Met Asp Lys Lys Leu Leu Ala 155 160 165 Pro Tyr Trp Thr Arg Pro Glu Arg Met Asp Lys Lys Leu Leu Wing 155 160 165

Val Pro Ala Ala Asn Thr Val Arg Phe Arg Cys Pro Ala Ala Gly 170 175 180 Val Pro Wing Wing Asn Thr Val Arg Phe Arg Cys Pro Wing Wing Gly 170 175 180

Asn Pro Thr Pro Ser Ile Ser Trp Leu Lys Asn Gly Arg Glu Phe 185 190 195 Asn Pro Thr Pro Ser Ile Ser Trp Leu Lys Asn Gly Arg Glu Phe 185 190 195

Arg Gly Glu His Arg Ile Gly Gly Ile Lys Leu Arg His Gln Gln 200 205 210 Arg Gly Glu His Arg Ile Gly Gly Ile Lys Leu Arg His Gln Gln 200 205 210

Trp Ser Leu Val Met Glu Ser Val Val Pro Ser Asp Arg Gly Asn 215 220 225 Trp Ser Leu Val Met Glu Ser Val Val Pro Ser Asp Arg Gly Asn 215 220 225

Tyr Thr Cys Val Val Glu Asn Lys Phe Gly Ser Ile Arg Gln Thr 230 235 240 Tyr Thr Cys Val Val Glu Asn Lys Phe Gly Ser Ile Arg Gln Thr 230 235 240

Tyr Thr Leu Asp Val Leu Glu Arg Ser Pro His Arg Pro Ile Leu 245 250 255 Tyr Thr Leu Asp Val Leu Glu Arg Ser Pro His Arg Pro Ile Leu 245 250 255

Gln Ala Gly Leu Pro Ala Asn Gln Thr Ala Val Leu Gly Ser Asp 260 265 270 Gln Wing Gly Leu Pro Wing Asn Gln Thr Wing Val Leu Gly Ser Asp 260 265 270

Val Glu Phe His Cys Lys Val Tyr Ser Asp Ala Gln Pro His Ile 275 280 285 Gln Trp Leu Lys His Val Glu Val Asn Gly Ser Lys Val Gly Pro 290 295 Val Glu Phe His Cys Lys Val Tyr Ser Asp Wing Gln Pro His Ile 275 280 285 Gln Trp Leu Lys His Val Glu Val Asn Gly Ser Lys Val Gly Pro 290 295

Asp Gly Thr Pro Tyr Val Thr Val Leu Lys Thr Ala Gly Ala Asn 305 310 315 Asp Gly Thr Pro Tyr Val Thr Val Leu Lys Thr Ala Gly Ala Asn 305 310 315

Thr Thr Asp Lys Glu Leu Glu Val Leu Ser Leu His Asn Val Thr 320 325 330 Thr Thr Asp Lys Glu Leu Glu Val Leu Ser Leu His Asn Val Thr 320 325 330

Phe Glu Asp Ala Gly Glu Tyr Thr Cys Leu Ala Gly Asn Ser Ile 335 340 345 Phe Glu Asp Wing Gly Glu Tyr Thr Cys Leu Wing Gly Asn Ser Ile 335 340 345

Gly Phe Ser His His Ser Ala Trp Leu Val Val Leu Pro Ala Glu 350 355 360 Gly Phe Ser His His Ser Wing Trp Leu Val Val Leu Pro Wing Glu 350 355 360

Glu Glu Leu Val Glu Ala Asp Glu Ala Gly Ser Val Tyr Ala Gly 365 370 375 Glu Glu Leu Val Glu Ala Asp Glu Ala Gly Ser Val Tyr Ala Gly 365 370 375

Ile Leu Ser Tyr Gly Val Gly Phe Phe Leu Phe Ile Leu Val Val 380 385 390 Ile Leu Ser Tyr Gly Val Gly Phe Phe Leu Phe Ile Leu Val Val 380 385 390

Ala Ala Val Thr Leu Cys Arg Leu Arg Ser Pro Pro Lys Lys Gly 395 400 405 Wing Wing Val Thr Leu Cys Arg Leu Arg Ser Pro Pro Lys Lys Gly 395 400 405

Leu Gly Ser Pro Thr Val His Lys Ile Ser Arg Phe Pro Leu Lys 410 415 420 Leu Gly Ser Pro Thr Val His Lys Ile Ser Arg Phe Pro Leu Lys 410 415 420

Arg Gln Val Ser Leu Glu Ser Asn Ala Ser Met Ser Ser Asn Thr 425 430 435 Arg Gln Val Be Leu Glu Be Asn Wing Be Met Be Be Asn Thr 425 430 435

Pro Leu Val Arg Ile Ala Arg Leu Ser Ser Gly Glu Gly Pro Thr 440 445 450 Pro Leu Val Arg Ile Ala Arg Leu Ser Be Gly Glu Gly Pro Thr 440 445 450

Leu Ala Asn Val Ser Glu Leu Glu Leu Pro Ala Asp Pro Lys Trp 455 460 465 Leu Wing Asn Val Ser Glu Leu Glu Leu Pro Wing Asp Pro Lys Trp 455 460 465

Glu Leu Ser Arg Ala Arg Leu Thr Leu Gly Lys Pro Leu Gly Glu 470 475 480 Glu Leu Ser Arg Ala Arg Leu Thr Leu Gly Lys Pro Leu Gly Glu 470 475 480

Gly Cys Phe Gly Gln Val Val Met Ala Glu Ala Ile Gly Ile Asp 485 490 495 Gly Cys Phe Gly Gln Val Val Met Wing Glu Wing Ile Gly Ile Asp 485 490 495

Lys Asp Arg Ala Ala Lys Pro Val Thr Val Ala Val Lys Met Leu 500 505 510 Lys Asp Arg Wing Wing Lys Pro Val Thr Val Wing Val Lys Met Leu 500 505 510

Lys Asp Asp Ala Thr Asp Lys Asp Leu Ser Asp Leu Val Ser Glu 515 520 525 Lys Asp Asp Wing Thr Asp Lys Asp Leu Ser Asp Leu Val Ser Glu 515 520 525

Met Glu Met Met Lys Met Ile Gly Lys His Lys Asn Ile Ile Asn 530 535 540 Met Glu Met Met Lys Met Ile Gly Lys His Lys Asn Ile Ile Asn 530 535 540

Leu Leu Gly Ala Cys Thr Gln Gly Gly Pro Leu Tyr Val Leu Val 545 550 555 Leu Leu Gly Ala Cys Thr Gln Gly Gly Pro Leu Tyr Val Leu Val 545 550 555

Glu Tyr Ala Ala Lys Gly Asn Leu Arg Glu Phe Leu Arg Ala Arg 560 565 570 Glu Tyr Ala Wing Lys Gly Asn Leu Arg Glu Phe Leu Arg Ala Arg 560 565 570

Arg Pro Pro Gly Leu Asp Tyr Ser Phe Asp Thr Cys Lys Pro Pro 575 580 585 Arg Pro Pro Gly Leu Asp Tyr Ser Phe Asp Thr Cys Lys Pro Pro 575 580 585

Glu Glu Gln Leu Thr Phe Lys Asp Leu Val Ser Cys Ala Tyr Gln 590 595 600 Glu Glu Gln Leu Thr Phe Lys Asp Leu Val Ser Cys Ala Tyr Gln 590 595 600

Val Ala Arg Gly Met Glu Tyr Leu Ala Ser Gln Lys Cys Ile His 605 610 615 Val Ala Arg Gly Met Glu Tyr Leu Ala Ser Gln Lys Cys Ile His 605 610 615

Arg Asp Leu Ala Ala Arg Asn Val Leu Val Thr Glu Asp Asn Val 620 625 Arg Asp Leu Wing Wing Arg Asn Val Leu Val Thr Glu Asp Asn Val 620 625

Met Lys Ile Ala Asp Phe Gly Leu Ala Arg Asp Val His Asn Leu 635 640 645 Met Lys Ile Wing Asp Phe Gly Leu Wing Arg Asp Val His Asn Leu 635 640 645

Asp Tyr Tyr Lys Lys Thr Thr Asn Gly Arg Leu Pro Val Lys Trp 650 655 660 Asp Tyr Tyr Lys Lys Thr Thr Asn Gly Arg Leu Pro Val Lys Trp 650 655 660

Met Ala Pro Glu Ala Leu Phe Asp Arg Val Tyr Thr His Gln Ser 665 670 675 Met Wing Pro Glu Wing Leu Phe Asp Arg Val Tyr Thr His Gln Ser 665 670 675

Asp Val Trp Ser Phe Gly Val Leu Leu Trp Glu Ile Phe Thr Leu 680 685 690 Asp Val Trp Ser Phe Gly Val Leu Leu Trp Glu Ile Phe Thr Leu 680 685 690

Gly Gly Ser Pro Tyr Pro Gly Ile Pro Val Glu Glu Leu Phe Lys 695 700 705 Gly Gly Ser Pro Tyr Pro Gly Ile Pro Val Glu Glu Leu Phe Lys 695 700 705

Leu Leu Lys Glu Gly His Arg Met Asp Lys Pro Ala Asn Cys Thr 710 715 720 Leu Leu Lys Glu Gly His Arg Met Asp Lys Pro Wing Asn Cys Thr 710 715 720

His Asp Leu Tyr Met Ile Met Arg Glu Cys Trp His Ala Ala Pro 725 730 735 His Asp Leu Tyr Met Ile Met Arg Glu Cys Trp His Ala Ala Pro 725 730 735

Ser Gln Arg Pro Thr Phe Lys Gln Leu Val Glu Asp Leu Asp Arg 740 745 750 Ser Gln Arg Pro Thr Phe Lys Gln Leu Val Glu Asp Leu Asp Arg 740 745 750

Val Leu Thr Val Thr Ser Thr Asp Glu Tyr Leu Asp Leu Ser Ala 755 760 765 Val Leu Thr Val Thr Ser Thr Asp Glu Tyr Leu Asp Leu Ser Ala 755 760 765

Pro Phe Glu Gln Tyr Ser Pro Gly Gly Gln Asp Thr Pro Ser Ser 770 775 780 Pro Phe Glu Gln Tyr Ser Pro Gly Gly Gln Asp Thr Pro Ser Ser 770 775 780

Ser Ser Ser Gly Asp Asp Ser Val Phe Ala His Asp Leu Leu Pro 785 790 795 Be Be Be Gly Asp Asp Be Val Phe Ala His Asp Leu Leu Pro 785 790 795

Pro Ala Pro Pro Ser Ser Gly Gly Ser Arg Thr 800 805 Pro Ala Pro Pro Ser Ser Gly Gly Ser Arg Thr 800 805

<210> 63 <210> 63

<211> 2549 <211> 2549

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 63 Met Leu Gly Thr Gly Pro Ala Ala Ala Thr Thr Ala Ala Thr Thr 1 5 10 15 <400> 63 Met Leu Gly Thr Gly Pro Wing Wing Thr Thr Wing Wing Thr Thr 1 5 10 15

Val Val Met Glu Met Ala Ser Lys Ala Ile Gly Arg Leu Ala Met Val Val Met Glu Met Wing Ser Lys Wing Ile Gly Arg Leu Wing Met

125 130 125 130

Val Gly Leu Leu Gly Tyr Ser Ser His Gln Gly Leu Met Gly Phe 335 340 345 Val Gly Leu Leu Gly Tyr Ser Ser His Gln Gly Leu Met Gly Phe 335 340 345

Tyr Leu Pro Arg Val Leu Asp Ile Ile Arg Ala Ala Leu Pro Pro 455 460 Tyr Leu Pro Arg Val Leu Asp Ile Ile Arg Wing Wing Leu Pro Pro 455 460

Lys Asp Phe Ala His Lys Arg Gln Lys Ala Met Gln Val Asp Ala 470 475 Lys Asp Phe Wing His Lys Arg Gln Lys Wing Met Gln Val Asp Wing 470 475

Val Val Gly Ile Thr Asp Pro Asp Pro Asp Ile Arg Tyr Cys Val 665 670 675 Val Val Gly Ile Thr Asp Pro Asp Pro Asp Ile Arg Tyr Cys Val 665 670 675

Leu Ala Ser Leu Asp Glu Arg Phe Asp Ala His Leu Ala Gln Ala 680 685 690 Leu Ala Ser Leu Asp Glu Arg Phe Asp Ala His Leu Gln Wing 680 685 690

Asn Asn Val Leu Ala Thr Ile Gly Glu Leu Ala Gln Val Ser Gly 800 805 Asn Asn Val Leu Wing Thr Ile Gly Glu Leu Wing Gln Val Ser Gly 800 805

Leu Glu Met Arg Lys Trp Val Asp Glu Leu Phe Ile Ile Ile Met 815 820 Leu Glu Met Arg Lys Trp Val Asp Glu Leu Phe Ile Ile Ile Met 815 820

Gly Ala Ile Arg Glu Phe Leu Phe Gln Gln Leu Gly Met Leu Val 1010 1015 1020 Gly Wing Ile Arg Glu Phe Leu Phe Gln Gln Leu Gly Met Leu Val 1010 1015 1020

Ser Phe Val Lys Ser His Ile Arg Pro Tyr Met Asp Glu Ile Val 1025 1030 1035 Ser Phe Val Lys Ser His Ile Arg Pro Tyr Met Asp Glu Ile Val 1025 1030 1035

Arg Leu Thr Glu Ser Leu Asp Phe Thr Asp Tyr Ala Ser Arg Ile Arg Leu Thr Glu Ser Leu Asp Phe Thr Asp Tyr Ala Ser Arg Ile

1145 1150 1145 1150

Ser Thr Ile Asn Leu Gln Lys Ala Trp Gly Ala Ala Arg Arg Val 1265 1270 1275 Ser Thr Ile Asn Leu Gln Lys Wing Trp Gly Wing Wing Arg Arg Val 1265 1270 1275

Ser Lys Asp Asp Trp Leu Glu Trp Leu Arg Arg Leu Ser Leu Glu 1280 1285 1290 Ser Lys Asp Asp Trp Leu Glu Trp Leu Arg Arg Leu Ser Leu Glu 1280 1285 1290

Leu Leu Lys Asp Ser Ser Ser Pro Ser Leu Arg Ser Cys Trp Ala 1295 1300 1305 Leu Leu Lys Asp Be Be Be Pro Be Leu Arg Be Cys Trp Wing 1295 1300 1305

Leu Ala Gln Ala Tyr Asn Pro Met Ala Arg Asp Leu Phe Asn Ala 1310 1315 1320 Leu Wing Gln Wing Tyr Asn Pro Met Wing Arg Asp Leu Phe Asn Wing 1310 1315 1320

Ala Phe Val Ser Cys Trp Ser Glu Leu Asn Glu Asp Gln Gln Asp 1325 1330 1335 Wing Phe Val Ser Cys Trp Ser Glu Leu Asn Glu Asp Gln Gln Asp 1325 1330 1335

Glu Leu Ile Arg Ser Ile Glu Leu Ala Leu Thr Ser Gln Asp Ile 1340 1345 1350 Glu Leu Ile Arg Ser Ile Glu Leu Ala Leu Thr Ser Gln Asp Ile 1340 1345 1350

Ala Glu Val Thr Gln Thr Leu Leu Asn Leu Ala Glu Phe Met Glu 1355 1360 1365 Wing Glu Val Thr Gln Thr Leu Leu Asn Leu Wing Glu Phe Met Glu 1355 1360 1365

His Ser Asp Lys Gly Pro Leu Pro Leu Arg Asp Asp Asn Gly Ile 1370 1375 1380 His Ser Asp Lys Gly Pro Leu Pro Leu Arg Asp Asp Asn Gly Ile 1370 1375 1380

Val Leu Leu Gly Glu Arg Ala Ala Lys Cys Arg Ala Tyr Ala Lys 1385 1390 1395 Val Leu Leu Gly Glu Arg Wing Lys Cys Arg Wing Tyr Wing Lys 1385 1390 1395

Ala Leu His Tyr Lys Glu Leu Glu Phe Gln Lys Gly Pro Thr Pro 1400 1405 1410 Ala Leu His Tyr Lys Glu Leu Glu Phe Gln Lys Gly Pro Thr Pro 1400 1405 1410

Ala Ile Leu Glu Ser Leu Ile Ser Ile Asn Asn Lys Leu Gln Gln 1415 1420 1425 Wing Ile Leu Glu Ser Leu Ile Ser Ile Asn Asn Lys Leu Gln Gln 1415 1420 1425

Pro Glu Ala Ala Ala Gly Val Leu Glu Tyr Ala Met Lys His Phe 1430 1435 1440 Pro Glu Wing Wing Gly Val Leu Glu Tyr Wing Met Lys His Phe 1430 1435 1440

Gly Glu Leu Glu Ile Gln Ala Thr Trp Tyr Glu Lys Leu His Glu 1445 1450 1455 Gly Glu Leu Glu Ile Gln Ala Thr Trp Tyr Glu Lys Leu His Glu 1445 1450 1455

Trp Glu Asp Ala Leu Val Ala Tyr Asp Lys Lys Met Asp Thr Asn 1460 1465 1470 Trp Glu Asp Wing Leu Val Wing Tyr Asp Lys Lys Met Asp Thr Asn 1460 1465 1470

Lys Asp Asp Pro Glu Leu Met Leu Gly Arg Met Arg Cys Leu Glu 1475 1480 1485 Ala Leu Gly Glu Trp Gly Gln Leu His Gln Gln Cys Cys Glu Lys 1490 1495 1500 Lys Asp Asp Pro Glu Leu Met Leu Gly Arg Met Arg Cys Leu Glu 1475 1480 1485 Ala Leu Gly Glu Trp Gly Gln Leu His Gln Gln Cys Cys Glu Lys 1490 1495 1500

Trp Thr Leu Val Asn Asp Glu Thr Gln Ala Lys Met Ala Arg Met 1505 1510 1515 Trp Thr Leu Val Asn Asp Glu Thr Gln Wing Lys Met Wing Arg Met 1505 1510 1515

Ala Ala Ala Ala Ala Trp Gly Leu Gly Gln Trp Asp Ser Met Glu 1520 1525 1530 Wing Wing Wing Wing Trp Gly Leu Gly Gln Trp Asp Ser Met Glu 1520 1525 1530

Glu Tyr Thr Cys Met Ile Pro Arg Asp Thr His Asp Gly Ala Phe 1535 1540 1545 Glu Tyr Thr Cys Met Ile Pro Arg Asp Thr His Asp Gly Ala Phe 1535 1540 1545

Tyr Arg Ala Val Leu Ala Leu His Gln Asp Leu Phe Ser Leu Ala 1550 1555 1560 Tyr Arg Wing Val Leu Wing Leu His Gln Asp Leu Phe Ser Leu Wing 1550 1555 1560

Gln Gln Cys Ile Asp Lys Ala Arg Asp Leu Leu Asp Ala Glu Leu 1565 1570 1575 Gln Gln Cys Ile Asp Lys Wing Arg Asp Leu Leu Asp Wing Glu Leu 1565 1570 1575

Thr Ala Met Ala Gly Glu Ser Tyr Ser Arg Ala Tyr Gly Ala Met 1580 1585 1590 Thr Wing Met Wing Gly Glu Ser Tyr Ser Arg Wing Tyr Gly Wing Met 1580 1585 1590

Val Ser Cys His Met Leu Ser Glu Leu Glu Glu Val Ile Gln Tyr 1595 1600 1605 Val Ser Cys His Met Leu Ser Glu Leu Glu Glu Val Ile Gln Tyr 1595 1600 1605

Lys Leu Val Pro Glu Arg Arg Glu Ile Ile Arg Gln Ile Trp Trp 1610 1615 1620 Lys Leu Val Pro Glu Arg Arg Glu Ile Ile Arg Gln Ile Trp Trp 1610 1615 1620

Glu Arg Leu Gln Gly Cys Gln Arg Ile Val Glu Asp Trp Gln Lys 1625 1630 1635 Glu Arg Leu Gln Gly Cys Gln Arg Ile Val Glu Asp Trp Gln Lys 1625 1630 1635

Ile Leu Met Val Arg Ser Leu Val Val Ser Pro His Glu Asp Met 1640 1645 1650 Ile Leu Met Val Arg Ser Leu Val Val Ser Pro His Glu Asp Met 1640 1645 1650

Arg Thr Trp Leu Lys Tyr Ala Ser Leu Cys Gly Lys Ser Gly Arg 1655 1660 1665 Arg Thr Trp Leu Lys Tyr Ala Ser Leu Cys Gly Lys Ser Gly Arg 1655 1660 1665

Leu Ala Leu Ala His Lys Thr Leu Val Leu Leu Leu Gly Val Asp 1670 1675 1680 Leu Ala Leu Ala His Lys Thr Leu Val Leu Leu Leu Gly Val Asp 1670 1675 1680

Pro Ser Arg Gln Leu Asp His Pro Leu Pro Thr Val His Pro Gln 1685 1690 1695 Pro Ser Arg Gln Leu Asp His Pro Leu Pro Thr Val His Pro Gln 1685 1690 1695

Val Thr Tyr Ala Tyr Met Lys Asn Met Trp Lys Ser Ala Arg Lys 1700 1705 1710 Val Thr Tyr Ala Tyr Met Lys Asn Met Trp Lys Ser Ala Arg Lys 1700 1705 1710

Ile Asp Ala Phe Gln His Met Gln His Phe Val Gln Thr Met Gln 1715 1720 1725 Ile Asp Ala Phe Gln His Met Gln His Phe Val Gln Thr Met Gln 1715 1720 1725

Gln Gln Ala Gln His Ala Ile Ala Thr Glu Asp Gln Gln His Lys 1730 1735 1740 Gln Gln Wing Gln His Wing Ile Wing Thr Glu Asp Gln Gln His Lys 1730 1735 1740

Gln Glu Leu His Lys Leu Met Ala Arg Cys Phe Leu Lys Leu Gly 1745 1750 1755 Gln Glu Leu His Lys Leu Met Ala Arg Cys Phe Leu Lys Leu Gly 1745 1750 1755

Glu Trp Gln Leu Asn Leu Gln Gly Ile Asn Glu Ser Thr Ile Pro 1760 1765 1770 Glu Trp Gln Leu Asn Leu Gln Gly Ile Asn Glu Ser Thr Ile Pro 1760 1765 1770

Lys Val Leu Gln Tyr Tyr Ser Ala Ala Thr Glu His Asp Arg Ser 1775 1780 1785 Lys Val Leu Gln Tyr Tyr Ser Ala Ala Thr Glu His Asp Arg Ser 1775 1780 1785

Trp Tyr Lys Ala Trp His Ala Trp Ala Val Met Asn Phe Glu Ala 1790 1795 1800 Trp Tyr Lys Wing Trp His Wing Trp Wing Val Met Asn Phe Glu Wing 1790 1795 1800

Val Leu His Tyr Lys His Gln Asn Gln Ala Arg Asp Glu Lys Lys 1805 1810 1815 Val Leu His Tyr Lys His Gln Asn Gln Ala Arg Asp Glu Lys Lys 1805 1810 1815

Lys Leu Arg His Ala Ser Gly Ala Asn Ile Thr Asn Ala Thr Thr 1820 1825 1830 Lys Leu Arg His Ala Ser Gly Ala Asn Ile Thr Asn Ala Thr Thr 1820 1825 1830

Ala Ala Thr Thr Ala Ala Thr Ala Thr Thr Thr Ala Ser Thr Glu 1835 1840 1845 Wing Thr Wing Thr Wing Thr Wing Thr Wing Thr Thr Wing Ser Thr Glu 1835 1840 1845

Gly Ser Asn Ser Glu Ser Glu Ala Glu Ser Thr Glu Asn Ser Pro 1850 1855 1860 Gly Ser Asn Ser Glu Ser Glu Ala Glu Ser Thr Glu Asn Ser Pro 1850 1855 1860

Thr Pro Ser Pro Leu Gln Lys Lys Val Thr Glu Asp Leu Ser Lys 1865 1870 1875 Thr Pro Ser Pro Leu Gln Lys Lys Val Thr Glu Asp Leu Ser Lys 1865 1870 1875

Thr Leu Leu Met Tyr Thr Val Pro Ala Val Gln Gly Phe Phe Arg 1880 1885 1890 Thr Leu Leu Met Tyr Thr Val Pro Wing Val Gln Gly Phe Phe Arg 1880 1885 1890

Ser Ile Ser Leu Ser Arg Gly Asn Asn Leu Gln Asp Thr Leu Arg 1895 1900 1905 Be Ile Be Leu Be Arg Gly Asn Asn Leu Gln Asp Thr Leu Arg 1895 1900 1905

Val Leu Thr Leu Trp Phe Asp Tyr Gly His Trp Pro Asp Val Asn 1910 1915 1920 Val Leu Thr Leu Trp Phe Asp Tyr Gly His Trp Pro Asp Val Asn 1910 1915 1920

Glu Ala Leu Val Glu Gly Val Lys Ala Ile Gln Ile Asp Thr Trp 1925 1930 1935 Glu Ala Leu Val Glu Gly Val Lys Ile Gln Ile Asp Thr Trp 1925 1930 1935

Leu Gln Val Ile Pro Gln Leu Ile Ala Arg Ile Asp Thr Pro Arg 1940 1945 1950 Leu Gln Val Ile Pro Gln Leu Ile Wing Arg Ile Asp Thr Pro Arg 1940 1945 1950

Pro Leu Val Gly Arg Leu Ile His Gln Leu Leu Thr Asp Ile Gly 1955 1960 1965 Pro Leu Val Gly Arg Leu Ile His Gln Leu Leu Thr Asp Ile Gly 1955 1960 1965

Arg Tyr His Pro Gln Ala Leu Ile Tyr Pro Leu Thr Val Ala Ser 1970 1975 1980 Arg Tyr His Pro Gln Ala Leu Ile Tyr Pro Leu Thr Val Ala Ser 1970 1975 1980

Lys Ser Thr Thr Thr Ala Arg His Asn Ala Ala Asn Lys Ile Leu 1985 1990 1995 Lys Ser Thr Thr Thr Ala Arg His Asn Ala Ala Asn Lys Ile Leu 1985 1990 1995

Lys Asn Met Cys Glu His Ser Asn Thr Leu Val Gln Gln Ala Met 2000 2005 2010 Lys Asn Met Cys Glu His Ser Asn Thr Leu Val Gln Gln Ala Met 2000 2005 2010

Met Val Ser Glu Glu Leu Ile Arg Val Ala Ile Leu Trp His Glu 2015 2020 2025 Met Val Ser Glu Glu Leu Ile Arg Val Ala Ile Leu Trp His Glu 2015 2020 2025

Met Trp His Glu Gly Leu Glu Glu Ala Ser Arg Leu Tyr Phe Gly 2030 2035 2040 Met Trp His Glu Gly Leu Glu Glu Ala Ser Arg Leu Tyr Phe Gly 2030 2035 2040

Glu Arg Asn Val Lys Gly Met Phe Glu Val Leu Glu Pro Leu His 2045 2050 2055 Glu Arg Asn Val Lys Gly Met Phe Glu Val Leu Glu Pro Leu His 2045 2050 2055

Ala Met Met Glu Arg Gly Pro Gln Thr Leu Lys Glu Thr Ser Phe 2060 2065 2070 Wing Met Met Glu Arg Gly Pro Gln Thr Leu Lys Glu Thr Ser Phe 2060 2065 2070

Asn Gln Ala Tyr Gly Arg Asp Leu Met Glu Ala Gln Glu Trp Cys 2075 2080 2085 Asn Gln Wing Tyr Gly Arg Asp Leu Met Glu Wing Gln Glu Trp Cys 2075 2080 2085

Arg Lys Tyr Met Lys Ser Gly Asn Val Lys Asp Leu Thr Gln Ala 2090 2095 2100 Arg Lys Tyr Met Lys Ser Gly Asn Val Lys Asp Leu Thr Gln Wing 2090 2095 2100

Trp Asp Leu Tyr Tyr His Val Phe Arg Arg Ile Ser Lys Gln Leu 2105 2110 2115 Trp Asp Leu Tyr Tyr His Val Phe Arg Arg Ile Ser Lys Gln Leu 2105 2110 2115

Pro Gln Leu Thr Ser Leu Glu Leu Gln Tyr Val Ser Pro Lys Leu 2120 2125 2130 Pro Gln Leu Thr Ser Leu Glu Leu Gln Tyr Val Ser Pro Lys Leu 2120 2125 2130

Leu Met Cys Arg Asp Leu Glu Leu Ala Val Pro Gly Thr Tyr Asp 2135 2140 2145 Leu Met Cys Arg Asp Leu Glu Leu Ala Val Pro Gly Thr Tyr Asp 2135 2140 2145

Pro Asn Gln Pro Ile Ile Arg Ile Gln Ser Ile Ala Pro Ser Leu 2150 2155 2160 Pro Asn Gln Pro Ile Ile Arg Ile Gln Ser Ile Ala Pro Ser Leu 2150 2155 2160

Gln Val Ile Thr Ser Lys Gln Arg Pro Arg Lys Leu Thr Leu Met Gln Val Ile Thr Ser Lys Gln Arg Pro Arg Lys Leu Thr Leu Met

2165 2170 2165 2170

Gly Ser Asn Gly His Glu Phe Val Phe Leu Leu Lys Gly His Glu 2180 2185 2190 Gly Ser Asn Gly His Glu Phe Val Phe Leu Leu Lys Gly His Glu 2180 2185 2190

Asp Leu Arg Gln Asp Glu Arg Val Met Gln Leu Phe Gly Leu Val 2195 2200 2205 Asp Leu Arg Gln Asp Glu Arg Val Met Gln Leu Phe Gly Leu Val 2195 2200 2205

Asn Thr Leu Leu Ala Asn Asp Pro Thr Ser Leu Arg Lys Asn Leu 2210 2215 2220 Asn Thr Leu Leu Wing Asn Asp Pro Thr Ser Leu Arg Lys Asn Leu 2210 2215 2220

Ser Ile Gln Arg Tyr Ala Val Ile Pro Leu Ser Thr Asn Ser Gly 2225 2230 2235 Ser Ile Gln Arg Tyr Ala Val Ile Pro Leu Ser Thr Asn Ser Gly 2225 2230 2235

Leu Ile Gly Trp Val Pro His Cys Asp Thr Leu His Ala Leu Ile 2240 2245 2250 Leu Ile Gly Trp Val Pro His Cys Asp Thr Leu His Ala Leu Ile 2240 2245 2250

Arg Asp Tyr Arg Glu Lys Lys Lys Ile Leu Leu Asn Ile Glu His 2255 2260 2265 Arg Asp Tyr Arg Glu Lys Lys Lys Ile Leu Leu Asn Ile Glu His 2255 2260 2265

Arg Ile Met Leu Arg Met Ala Pro Asp Tyr Asp His Leu Thr Leu 2270 2275 2280 Arg Ile Met Leu Arg Met Ala Pro Asp Tyr Asp His Leu Thr Leu 2270 2275 2280

Met Gln Lys Val Glu Val Phe Glu His Ala Val Asn Asn Thr Ala 2285 2290 2295 Met Gln Lys Val Glu Val Phe Glu His Ala Val Asn Asn Thr Ala 2285 2290 2295

Gly Asp Asp Leu Ala Lys Leu Leu Trp Leu Lys Ser Pro Ser Ser 2300 2305 2310 Gly Asp Asp Leu Ala Lys Leu Leu Trp Leu Lys Ser Pro Ser Ser 2300 2305 2310

Glu Val Trp Phe Asp Arg Arg Thr Asn Tyr Thr Arg Ser Leu Ala 2315 2320 2325 Glu Val Trp Phe Asp Arg Arg Thr Asn Tyr Thr Arg Ser Leu Ala 2315 2320 2325

Val Met Ser Met Val Gly Tyr Ile Leu Gly Leu Gly Asp Arg His 2330 2335 2340 Val Met Ser Met Val Gly Tyr Ile Leu Gly Leu Gly Asp Arg His 2330 2335 2340

Pro Ser Asn Leu Met Leu Asp Arg Leu Ser Gly Lys Ile Leu His 2345 2350 2355 Pro Ser Asn Leu Met Leu Asp Arg Leu Ser Gly Lys Ile Leu His 2345 2350 2355

Ile Asp Phe Gly Asp Cys Phe Glu Val Ala Met Thr Arg Glu Lys 2360 2365 2370 Ile Asp Phe Gly Asp Cys Phe Glu Val Wing Met Thr Arg Glu Lys 2360 2365 2370

Phe Pro Glu Lys Ile Pro Phe Arg Leu Thr Arg Met Leu Thr Asn 2375 2380 2385 Phe Pro Glu Lys Ile Pro Phe Arg Leu Thr Arg Met Leu Thr Asn 2375 2380 2385

Ala Met Glu Val Thr Gly Leu Asp Gly Asn Tyr Arg Ile Thr Cys 2390 2395 2400 Wing Met Glu Val Thr Gly Leu Asp Gly Asn Tyr Arg Ile Thr Cys 2390 2395 2400

His Thr Val Met Glu Val Leu Arg Glu His Lys Asp Ser Val Met 2405 2410 2415 His Thr Val Met Glu Val Leu Arg Glu His Lys Asp Ser Val Met 2405 2410 2415

Ala Val Leu Glu Ala Phe Val Tyr Asp Pro Leu Leu Asn Trp Arg 2420 2425 2430 Wing Val Leu Glu Wing Phe Val Tyr Asp Pro Leu Leu Asn Trp Arg 2420 2425 2430

Leu Met Asp Thr Asn Thr Lys Gly Asn Lys Arg Ser Arg Thr Arg 2435 2440 2445 Leu Met Asp Thr Asn Thr Lys Gly Asn Lys Arg Ser Arg Thr Arg 2435 2440 2445

Thr Asp Ser Tyr Ser Ala Gly Gln Ser Val Glu Ile Leu Asp Gly 2450 2455 2460 Thr Asp Ser Tyr Ser Ala Gly Gln Ser Val Glu Ile Leu Asp Gly 2450 2455 2460

Val Glu Leu Gly Glu Pro Ala His Lys Lys Thr Gly Thr Thr Val 2465 2470 2475 Val Glu Leu Gly Glu Pro Ala His Lys Lys Thr Gly Thr Thr Val 2465 2470 2475

Pro Glu Ser Ile His Ser Phe Ile Gly Asp Gly Leu Val Lys Pro 2480 2485 2490 Pro Glu Ser Ile His Ser Phe Ile Gly Asp Gly Leu Val Lys Pro 2480 2485 2490

Glu Ala Leu Asn Lys Lys Ala Ile Gln Ile Ile Asn Arg Val Arg 2495 2500 2505 Glu Wing Leu Asn Lys Lys Wing Ile Gln Ile Ile Asn Arg Val Arg 2495 2500 2505

Asp Lys Leu Thr Gly Arg Asp Phe Ser His Asp Asp Thr Leu Asp 2510 2515 2520 Asp Lys Leu Thr Gly Arg Asp Phe Ser His Asp Asp Thr Leu Asp 2510 2515 2520

Val Pro Thr Gln Val Glu Leu Leu Ile Lys Gln Ala Thr Ser His 2525 2530 2535 Val Pro Thr Gln Val Glu Leu Leu Ile Lys Gln Ala Thr Ser His 2525 2530 2535

Glu Asn Leu Cys Gln Cys Tyr Ile Gly Trp Cys Pro Phe Trp 2540 2545 Glu Asn Leu Cys Gln Cys Tyr Ile Gly Trp Cys Pro Phe Trp 2540 2545

<210> 64 <210> 64

<211> 1356 <211> 1356

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 64 Met Gln Ser Lys Val Leu Leu Ala Val Ala Leu Trp Leu Cys Val 1 5 10 15 <400> 64 Met Gln Ser Lys Val Leu Leu Val Wing Leu Trp Leu Cys Val 1 5 10 15

Arg Glu Thr Asp Leu Ala Ser Val Ile Tyr Val Tyr Val Gln Asp 110 115 120 Arg Glu Thr Asp Leu Ala Ser Val Ile Tyr Val Tyr Val Gln Asp 110 115 120

Tyr Arg Ser Pro Phe Ile Ala Ser Val Ser Asp Gln His Gly Val 125 130 135 Tyr Arg Ser Pro Phe Ile Ala Ser Val Ser Asp Gln His Gly Val 125 130 135

Ile Asp Phe Asn Trp Glu Tyr Pro Ser Ser Lys His Gln His Lys 260 265 270 Lys Leu Val Asn Arg Asp Leu Lys Thr Gln Ser Gly Ser Glu Met 275 280 Ile Asp Phe Asn Trp Glu Tyr Pro Ser Ser Lys His Gln His Lys 260 265 270 Lys Leu Val Asn Arg Asp Leu Lys Thr Gln Ser Gly Ser Glu Met 275 280

Pro Pro Pro His His Ile His Trp Tyr Trp Gln Leu Glu Glu Glu 455 460 465 Pro Pro Pro His His Ile His Trp Tyr Trp Gln Leu Glu Glu Glu 455 460 465

Cys Ala Asn Glu Pro Ser Gln Ala Val Ser Val Thr Asn Pro Tyr 470 475 480 Cys Ala Asn Glu Pro Ser Gln Ala Val Ser Val Thr Asn Pro Tyr 470 475 480

Pro Val Cys Lys Asn Leu Asp Thr Leu Trp Lys Leu Asn Ala Thr Pro Val Cys Lys Asn Leu Asp Thr Leu Trp Lys Leu Asn Ala Thr

605 610 605 610

Glu Leu Lys Thr Gly Tyr Leu Ser Ile Val Met Asp Pro Asp Glu 800 805 810 Glu Leu Lys Thr Gly Tyr Leu Ser Ile Val Met Asp Pro Asp Glu 800 805 810

Lys Arg Asn Glu Phe Val Pro Tyr Lys Thr Lys Gly Ala Arg Phe 935 940 Lys Arg Asn Glu Phe Val Pro Tyr Lys Thr Lys Gly Ala Arg Phe 935 940

Arg Gln Gly Lys Asp Tyr Val Gly Ala Ile Pro Val Asp Leu Lys 950 955 Arg Gln Gly Lys Asp Tyr Val Gly Wing Ile Pro Val Asp Leu Lys 950 955

Leu Ser Ser Pro Pro Val 1355 Leu Ser Ser Pro Pro Val 1355

<210> 65 <210> 65

<211> 400 <211> 400

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 65 Met Leu Ala Arg Arg Lys Pro Val Leu Pro Ala Leu Thr Ile Asn 1 5 10 15 <400> 65 Met Leu Wing Arg Arg Lys Pro Val Leu Pro Wing Leu Thr Ile Asn 1 5 10 15

Pro Thr Ile Ala Glu Gly Pro Ser Pro Thr Ser Glu Gly Ala Ser 20 25 30 Pro Thr Ile Wing Glu Gly Pro Ser Pro Thr Ser Glu Gly Ala Ser 20 25 30

Glu Ala Asn Leu Val Asp Leu Gln Lys Lys Leu Glu Glu Leu Glu 35 40 45 Glu Ala Asn Leu Val Asp Leu Gln Lys Lys Leu Glu Glu Leu Glu 35 40 45

Leu Asp Glu Gln Gln Lys Lys Arg Leu Glu Ala Phe Leu Thr Gln 50 55 60 Leu Asp Glu Gln Gln Lys Lys Arg Leu Glu Ala Phe Leu Thr Gln 50 55 60

Lys Ala Lys Val Gly Glu Leu Lys Asp Asp Asp Phe Glu Arg Ile 65 70 75 Lys Wing Lys Val Gly Glu Leu Lys Asp Asp Asp Phe Glu Arg Ile 65 70 75

Ser Glu Leu Gly Ala Gly Asn Gly Gly Val Val Thr Lys Val Gln 80 85 90 Ser Glu Leu Gly Ala Gly Asn Gly Gly Val Val Thr Lys Val Gln 80 85 90

His Arg Pro Ser Gly Leu Ile Met Ala Arg Lys Leu Ile His Leu 95 100 105 His Arg Pro Ser Gly Leu Ile Met Ala Arg Lys Leu Ile His Leu 95 100 105

Glu Ile Lys Pro Ala Ile Arg Asn Gln Ile Ile Arg Glu Leu Gln 110 115 120 Glu Ile Lys Pro Wing Ile Arg Asn Gln Ile Ile Arg Glu Leu Gln 110 115 120

Val Leu His Glu Cys Asn Ser Pro Tyr Ile Val Gly Phe Tyr Gly 125 130 135 Val Leu His Glu Cys Asn Ser Pro Tyr Ile Val Gly Phe Tyr Gly 125 130 135

Ala Phe Tyr Ser Asp Gly Glu Ile Ser Ile Cys Met Glu His Met 140 145 150 Wing Phe Tyr Ser Asp Gly Glu Ile Ser Ile Cys Met Glu His Met 140 145 150

Asp Gly Gly Ser Leu Asp Gln Val Leu Lys Glu Ala Lys Arg Ile 155 160 165 Asp Gly Gly Ser Leu Asp Gln Val Leu Lys Glu Ala Lys Arg Ile 155 160 165

Pro Glu Glu Ile Leu Gly Lys Val Ser Ile Ala Val Leu Arg Gly 170 175 180 Pro Glu Glu Ile Leu Gly Lys Val Ser Ile Ala Val Leu Arg Gly 170 175 180

Leu Ala Tyr Leu Arg Glu Lys His Gln Ile Met His Arg Asp Val 185 190 195 Leu Ala Tyr Leu Arg Glu Lys His Gln Ile Met His Arg Asp Val 185 190 195

Lys Pro Ser Asn Ile Leu Val Asn Ser Arg Gly Glu Ile Lys Leu 200 205 210 Lys Pro Ser Asn Ile Leu Val Asn Ser Arg Gly Glu Ile Lys Leu 200 205 210

Cys Asp Phe Gly Val Ser Gly Gln Leu Ile Asp Ser Met Ala Asn 215 220 225 Cys Asp Phe Gly Val Ser Gly Gln Leu Ile Asp Ser Met Ala Asn 215 220 225

Ser Phe Val Gly Thr Arg Ser Tyr Met Ala Pro Glu Arg Leu Gln 230 235 240 Ser Phe Val Gly Thr Arg Ser Tyr Met Ala Pro Glu Arg Leu Gln 230 235 240

Gly Thr His Tyr Ser Val Gln Ser Asp Ile Trp Ser Met Gly Leu 245 250 255 Gly Thr His Tyr Ser Val Gln Ser Asp Ile Trp Ser Met Gly Leu 245 250 255

Ser Leu Val Glu Leu Ala Val Gly Arg Tyr Pro Ile Pro Pro Pro 260 265 270 Ser Leu Val Glu Leu Ala Val Gly Arg Tyr Pro Ile Pro Pro Pro 260 265 270

Asp Ala Lys Glu Leu Glu Ala Ile Phe Gly Arg Pro Val Val Asp 275 280 285 Asp Wing Lys Glu Leu Glu Wing Ile Phe Gly Arg Pro Val Val Asp 275 280 285

Gly Glu Glu Gly Glu Pro His Ser Ile Ser Pro Arg Pro Arg Pro 290 295 300 Gly Glu Glu Gly Glu Pro His Ser Ile Ser Pro Arg Pro Arg Pro 290 295 300

Pro Gly Arg Pro Val Ser Gly His Gly Met Asp Ser Arg Pro Ala 305 310 315 Pro Gly Arg Pro Val Ser Gly His Gly Met Asp Ser Arg Pro Wing 305 310 315

Met Ala Ile Phe Glu Leu Leu Asp Tyr Ile Val Asn Glu Pro Pro 320 325 330 Met Ile Phe Glu Leu Leu Asp Tyr Ile Val Asn Glu Pro Pro 320 325 330

Pro Lys Leu Pro Asn Gly Val Phe Thr Pro Asp Phe Gln Glu Phe 335 340 345 Pro Lys Leu Pro Asn Gly Val Phe Thr Pro Asp Phe Gln Glu Phe 335 340 345

Val Asn Lys Cys Leu Ile Lys Asn Pro Ala Glu Arg Ala Asp Leu 350 355 360 Val Asn Lys Cys Leu Ile Lys Asn Pro Wing Glu Arg Wing Asp Leu 350 355 360

Lys Met Leu Thr Asn His Thr Phe Ile Lys Arg Ser Glu Val Glu 365 370 375 Lys Met Leu Thr Asn His Thr Phe Ile Lys Arg Ser Glu Val Glu 365 370 375

Glu Val Asp Phe Ala Gly Trp Leu Cys Lys Thr Leu Arg Leu Asn 380 385 390 Glu Val Asp Phe Ala Gly Trp Leu Cys Lys Thr Leu Arg Leu Asn 380 385 390

Gln Pro Gly Thr Pro Thr Arg Thr Ala Val 395 400 Gln Pro Gly Thr Pro Thr Arg Thr Ala Val 395 400

<210> 66 <210> 66

<211> 1390 <211> 1390

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 66 Met Lys Ala Pro Ala Val Leu Ala Pro Gly Ile Leu Val Leu Leu 1 5 10 15 <400> 66 Met Lys Pro Wing Val Leu Wing Pro Gly Ile Leu Val Leu Leu 1 5 10 15

Glu Asp Leu Gln Lys Val Ala Glu Tyr Lys Thr Gly Pro Val Leu 80 85 90 Glu Asp Leu Gln Lys Val Wing Glu Tyr Lys Thr Gly Pro Val Leu 80 85 90

Glu His Pro Asp Cys Phe Pro Cys Gln Asp Cys Ser Ser Lys Ala 95 100 105 Glu His Pro Asp Cys Phe Pro Cys Gln Asp Cys Ser Ser Lys Ala 95 100 105

Val Val Asp Thr Tyr Tyr Asp Asp Gln Leu Ile Ser Cys Gly Ser 125 130 135 Val Asn Arg Gly Thr Cys Gln Arg His Val Phe Pro His Asn His 140 145 Val Val Asp Thr Tyr Tyr Asp Asp Gln Leu Ile Ser Cys Gly Ser 125 130 135 Val Asn Arg Gly Thr Cys Gln Arg His Val Phe Pro His Asn His 140 145

Thr Thr Ala Leu Gln Arg Val Asp Leu Phe Met Gly Gln Phe Ser 425 430 435 Thr Thr Ala Leu Gln Arg Val Asp Leu Phe Met Gly Gln Phe Ser 425 430 435

Val Val Ser Arg Ser Gly Pro Ser Thr Pro His Val Asn Phe Leu 470 475 Val Val Ser Arg Ser Gly Pro Ser Thr Pro His Val Asn Phe Leu 470 475

Leu Asp Ser His Pro Val Ser Pro Glu Val Ile Val Glu His Thr 485 490 Leu Asp Ser His Pro Val Ser Pro Glu Val Ile Val Glu His Thr 485 490

Lys Ser Phe Ile Ser Gly Gly Ser Thr Ile Thr Gly Val Gly Lys 755 760 765 Lys Ser Phe Ile Ser Gly Gly Ser Thr Ile Thr Gly Val Gly Lys 755 760 765

Asn Leu Asn Ser Val Ser Val Pro Arg Met Val Ile Asn Val His 770 775 780 Asn Leu Asn Ser Val Ser Val Pro Arg Met Val Ile Asn Val His 770 775 780

Glu Ala Gly Arg Asn Phe Thr Val Ala Cys Gln His Arg Ser Asn 785 790 795 Glu Ala Gly Arg Asn Phe Thr Val Ala Cys Gln His Arg Ser Asn 785 790 795

Ser Glu Ile Ile Cys Cys Thr Thr Pro Ser Leu Gln Gln Leu Asn 800 805 810 Ser Glu Ile Ile Cys Cys Thr Thr Pro Ser Leu Gln Gln Leu Asn 800 805 810

Leu Gln Leu Pro Leu Lys Thr Lys Ala Phe Phe Met Leu Asp Gly Leu Gln Leu Pro Leu Lys Thr Lys Wing Phe Phe Met Leu Asp Gly

815 820 815 820

Ile Leu Ser Lys Tyr Phe Asp Leu Ile Tyr Val His Asn Pro Val 830 835 840 Ile Leu Ser Lys Tyr Phe Asp Leu Ile Tyr Val His Asn Pro Val 830 835 840

Phe Lys Pro Phe Glu Lys Pro Val Met Ile Ser Met Gly Asn Glu 845 850 855 Phe Lys Pro Phe Glu Lys Pro Val Met Ile Ser Met Gly Asn Glu 845 850 855

Asn Val Leu Glu Ile Lys Gly Asn Asp Ile Asp Pro Glu Ala Val 860 865 870 Asn Val Leu Glu Ile Lys Gly Asn Asp Ile Asp Pro Glu Ala Val 860 865 870

Lys Gly Glu Val Leu Lys Val Gly Asn Lys Ser Cys Glu Asn Ile 875 880 885 Lys Gly Glu Val Leu Lys Val Gly Asn Lys Ser Cys Glu Asn Ile 875 880 885

His Leu His Ser Glu Ala Val Leu Cys Thr Val Pro Asn Asp Leu 890 895 900 His Leu His Ser Glu Ala Val Leu Cys Thr Val Pro Asn Asp Leu 890 895 900

Leu Lys Leu Asn Ser Glu Leu Asn Ile Glu Trp Lys Gln Ala Ile 905 910 915 Leu Lys Leu Asn Ser Glu Leu Asn Ile Glu Trp Lys Gln Ile Wing 905 910 915

Ser Ser Thr Val Leu Gly Lys Val Ile Val Gln Pro Asp Gln Asn 920 925 930 Ser Ser Thr Val Leu Gly Lys Val Ile Val Gln Pro Asp Gln Asn 920 925 930

Phe Thr Gly Leu Ile Ala Gly Val Val Ser Ile Ser Thr Ala Leu 935 940 945 Phe Thr Gly Leu Ile Wing Gly Val Val Ser Ile Ser Thr Ala Leu 935 940 945

Leu Leu Leu Leu Gly Phe Phe Leu Trp Leu Lys Lys Arg Lys Gln 950 955 960 Leu Leu Leu Leu Gly Phe Phe Leu Trp Leu Lys Lys Arg Lys Gln 950 955 960

Ile Lys Asp Leu Gly Ser Glu Leu Val Arg Tyr Asp Ala Arg Val 965 970 975 Ile Lys Asp Leu Gly Ser Glu Leu Val Arg Tyr Asp Ala Arg Val 965 970 975

His Thr Pro His Leu Asp Arg Leu Val Ser Ala Arg Ser Val Ser 980 985 990 His Thr Pro His Leu Asp Arg Leu Val Ser Ala Arg Ser Val Ser 980 985 990

Pro Thr Thr Glu Met Val Ser Asn Glu Ser Val Asp Tyr Arg Ala 995 1000 1005 Pro Thr Thr Glu Met Val Ser Asn Glu Ser Val Asp Tyr Arg Wing 995 1000 1005

Thr Phe Pro Glu Asp Gln Phe Pro Asn Ser Ser Gln Asn Gly Ser 1010 1015 1020 Thr Phe Pro Glu Asp Gln Phe Pro Asn Ser Ser Gln Asn Gly Ser 1010 1015 1020

Cys Arg Gln Val Gln Tyr Pro Leu Thr Asp Met Ser Pro Ile Leu 1025 1030 1035 Cys Arg Gln Val Gln Tyr Pro Leu Thr Asp Met Ser Pro Ile Leu 1025 1030 1035

Thr Ser Gly Asp Ser Asp Ile Ser Ser Pro Leu Leu Gln Asn Thr 1040 1045 1050 Thr Be Gly Asp Be Asp Ile Be Be Pro Leu Leu Gln Asn Thr 1040 1045 1050

Val His Ile Asp Leu Ser Ala Leu Asn Pro Glu Leu Val Gln Ala 1055 1060 1065 Val His Ile Asp Leu Ser Ala Leu Asn Pro Glu Leu Val Gln Ala 1055 1060 1065

Val Gln His Val Val Ile Gly Pro Ser Ser Leu Ile Val His Phe 1070 1075 1080 Val Gln His Val Val Ile Gly Pro Ser Ser Leu Ile Val His Phe 1070 1075 1080

Asn Glu Val Ile Gly Arg Gly His Phe Gly Cys Val Tyr His Gly 1085 1090 1095 Asn Glu Val Ile Gly Arg Gly His Phe Gly Cys Val Tyr His Gly 1085 1090 1095

Thr Leu Leu Asp Asn Asp Gly Lys Lys Ile His Cys Ala Val Lys 1100 1105 1110 Thr Leu Leu Asp Asn Asp Gly Lys Lys Ile His Cys Ala Val Lys 1100 1105 1110

Ser Leu Asn Arg Ile Thr Asp Ile Gly Glu Val Ser Gln Phe Leu 1115 1120 1125 Ser Leu Asn Arg Ile Thr Asp Ile Gly Glu Val Ser Gln Phe Leu 1115 1120 1125

Thr Glu Gly Ile Ile Met Lys Asp Phe Ser His Pro Asn Val Leu 1130 1135 1140 Thr Glu Gly Ile Ile Met Lys Asp Phe Ser His Pro Asn Val Leu 1130 1135 1140

Ser Leu Leu Gly Ile Cys Leu Arg Ser Glu Gly Ser Pro Leu Val 1145 1150 1155 Ser Leu Leu Gly Ile Cys Leu Arg Ser Glu Gly Ser Pro Leu Val 1145 1150 1155

Val Leu Pro Tyr Met Lys His Gly Asp Leu Arg Asn Phe Ile Arg 1160 1165 1170 Val Leu Pro Tyr Met Lys His Gly Asp Leu Arg Asn Phe Ile Arg 1160 1165 1170

Asn Glu Thr His Asn Pro Thr Val Lys Asp Leu Ile Gly Phe Gly 1175 1180 1185 Asn Glu Thr His Asn Pro Thr Val Lys Asp Leu Ile Gly Phe Gly 1175 1180 1185

Leu Gln Val Ala Lys Gly Met Lys Tyr Leu Ala Ser Lys Lys Phe 1190 1195 1200 Leu Gln Val Wing Lys Gly Met Lys Tyr Leu Wing Ser Lys Lys Phe 1190 1195 1200

Val His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu Asp Glu Lys 1205 1210 1215 Val His Arg Asp Leu Ala Wing Arg Asn Cys Met Leu Asp Glu Lys 1205 1210 1215

Phe Thr Val Lys Val Ala Asp Phe Gly Leu Ala Arg Asp Met Tyr 1220 1225 1230 Phe Thr Val Lys Val Wing Asp Phe Gly Leu Wing Arg Asp Met Tyr 1220 1225 1230

Asp Lys Glu Tyr Tyr Ser Val His Asn Lys Thr Gly Ala Lys Leu 1235 1240 1245 Asp Lys Glu Tyr Tyr Ser Val His Asn Lys Thr Gly Ala Lys Leu 1235 1240 1245

Pro Val Lys Trp Met Ala Leu Glu Ser Leu Gln Thr Gln Lys Phe 1250 1255 1260 Pro Val Lys Trp Met Ala Leu Glu Ser Leu Gln Thr Gln Lys Phe 1250 1255 1260

Thr Thr Lys Ser Asp Val Trp Ser Phe Gly Val Leu Leu Trp Glu 1265 1270 1275 Thr Thr Lys Ser Asp Val Trp Ser Phe Gly Val Leu Leu Trp Glu 1265 1270 1275

Leu Met Thr Arg Gly Ala Pro Pro Tyr Pro Asp Val Asn Thr Phe 1280 1285 1290 Leu Met Thr Arg Gly Ala Pro Pro Tyr Pro Asp Val Asn Thr Phe 1280 1285 1290

Asp Ile Thr Val Tyr Leu Leu Gln Gly Arg Arg Leu Leu Gln Pro 1295 1300 1305 Asp Ile Thr Val Tyr Leu Leu Gln Gly Arg Arg Leu Leu Gln Pro 1295 1300 1305

Glu Tyr Cys Pro Asp Pro Leu Tyr Glu Val Met Leu Lys Cys Trp 1310 1315 1320 Glu Tyr Cys Pro Asp Pro Leu Tyr Glu Val Met Leu Lys Cys Trp 1310 1315 1320

His Pro Lys Ala Glu Met Arg Pro Ser Phe Ser Glu Leu Val Ser 1325 1330 1335 His Pro Lys Wing Glu Met Arg Pro Ser Phe Ser Glu Leu Val Ser 1325 1330 1335

Arg Ile Ser Ala Ile Phe Ser Thr Phe Ile Gly Glu His Tyr Val 1340 1345 1350 Arg Ile Ser Ala Ile Phe Ser Thr Phe Ile Gly Glu His Tyr Val 1340 1345 1350

His Val Asn Ala Thr Tyr Val Asn Val Lys Cys Val Ala Pro Tyr 1355 1360 1365 His Val Asn Wing Thr Tyr Val Asn Val Lys Cys Val Wing Pro Tyr 1355 1360 1365

Pro Ser Leu Leu Ser Ser Glu Asp Asn Ala Asp Asp Glu Val Asp 1370 1375 1380 Pro Ser Leu Leu Ser Ser Glu Asp Asn Ala Asp Asp Glu Val Asp 1370 1375 1380

Thr Arg Pro Ala Ser Phe Trp Glu Thr Ser 1385 1390 Thr Arg Pro Ala Ser Phe Trp Glu Thr Ser 1385 1390

<210> 67 <210> 67

<211> 1068 <211> 1068

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 67 Met Pro Pro Arg Pro Ser Ser Gly Glu Leu Trp Gly Ile His Leu 1 5 10 15 <400> 67 Met Pro Pro Arg Pro Ser Ser Gly Glu Leu Trp Gly Ile His Leu 1 5 10 15

Met Pro Pro Arg Ile Leu Val Glu Cys Leu Leu Pro Asn Gly Met 20 25 30 Met Pro Pro Arg Ile Leu Val Glu Cys Leu Leu Pro Asn Gly Met 20 25 30

Ile Val Thr Leu Glu Cys Leu Arg Glu Ala Thr Leu Ile Thr Ile 35 40 45 Ile Val Thr Leu Glu Cys Leu Arg Glu Ala Thr Leu Ile Thr Ile 35 40 45

Lys His Glu Leu Phe Lys Glu Ala Arg Lys Tyr Pro Leu His Gln 50 55 60 Lys His Glu Leu Phe Lys Glu Ala Arg Lys Tyr Pro Leu His Gln 50 55 60

Leu Leu Gln Asp Glu Ser Ser Tyr Ile Phe Val Ser Val Thr Gln 65 70 75 Glu Ala Glu Arg Glu Glu Phe Phe Asp Glu Thr Arg Arg Leu Cys 80 85 Leu Leu Gln Asp Glu Ser Be Tyr Ile Phe Val Ser Val Thr Gln 65 70 75 Glu Ala Glu Arg Glu Glu Phe Phe Asp Glu Thr Arg Arg Leu Cys 80 85

Asp Leu Arg Leu Phe Gln Pro Phe Leu Lys Val Ile Glu Pro Val 95 100 105 Asp Leu Arg Leu Phe Gln Pro Phe Leu Lys Val Ile Glu Pro Val 95 100 105

Gly Asn Arg Glu Glu Lys Ile Leu Asn Arg Glu Ile Gly Phe Ala 110 115 120 Gly Asn Arg Glu Glu Lys Ile Leu Asn Arg Glu Ile Gly Phe Ala 110 115 120

Ile Gly Met Pro Val Cys Glu Phe Asp Met Val Lys Asp Pro Glu 125 130 135 Ile Gly Met Pro Val Cys Glu Phe Asp Met Val Lys Asp Pro Glu 125 130 135

Val Gln Asp Phe Arg Arg Asn Ile Leu Asn Val Cys Lys Glu Ala 140 145 150 Val Gln Asp Phe Arg Arg Asn Ile Leu Asn Val Cys Lys Glu Ala 140 145 150

Val Asp Leu Arg Asp Leu Asn Ser Pro His Ser Arg Ala Met Tyr 155 160 165 Val Asp Leu Arg Asp Leu Asn Ser Pro His Ser Arg Ala Met Tyr 155 160 165

Val Tyr Pro Pro Asn Val Glu Ser Ser Pro Glu Leu Pro Lys His 170 175 180 Val Tyr Pro Pro Asn Val Glu Ser Ser Pro Glu Leu Pro Lys His 170 175 180

Ile Tyr Asn Lys Leu Asp Lys Gly Gln Ile Ile Val Val Ile Trp 185 190 195 Ile Tyr Asn Lys Leu Asp Lys Gly Gln Ile Ile Val Val Ile Trp 185 190 195

Val Ile Val Ser Pro Asn Asn Asp Lys Gln Lys Tyr Thr Leu Lys 200 205 210 Val Ile Val Ser Pro Asn Asn Asp Lys Gln Lys Tyr Thr Leu Lys 200 205 210

Ile Asn His Asp Cys Val Pro Glu Gln Val Ile Ala Glu Ala Ile 215 220 225 Ile Asn His Asp Cys Val Pro Glu Gln Val Ile Wing Glu Ile Wing 215 220 225

Arg Lys Lys Thr Arg Ser Met Leu Leu Ser Ser Glu Gln Leu Lys 230 235 240 Arg Lys Lys Thr Arg Ser Met Leu Leu Ser Ser Glu Gln Leu Lys 230 235 240

Leu Cys Val Leu Glu Tyr Gln Gly Lys Tyr Ile Leu Lys Val Cys 245 250 255 Leu Cys Val Leu Glu Tyr Gln Gly Lys Tyr Ile Leu Lys Val Cys 245 250 255

Gly Cys Asp Glu Tyr Phe Leu Glu Lys Tyr Pro Leu Ser Gln Tyr 260 265 270 Gly Cys Asp Glu Tyr Phe Leu Glu Lys Tyr Pro Leu Ser Gln Tyr 260 265 270

Lys Tyr Ile Arg Ser Cys Ile Met Leu Gly Arg Met Pro Asn Leu 275 280 285 Lys Tyr Ile Arg Ser Cys Ile Met Leu Gly Arg Met Pro Asn Leu 275 280 285

Met Leu Met Ala Lys Glu Ser Leu Tyr Ser Gln Leu Pro Met Asp 290 295 300 Met Leu Met Wing Lys Glu Ser Leu Tyr Ser Gln Leu Pro Met Asp 290 295 300

Cys Phe Thr Met Pro Ser Tyr Ser Arg Arg Ile Ser Thr Ala Thr 305 310 315 Cys Phe Thr Met Pro Ser Tyr Ser Arg Arg Ile Ser Thr Ala Thr 305 310 315

Pro Tyr Met Asn Gly Glu Thr Ser Thr Lys Ser Leu Trp Val Ile 320 325 330 Pro Tyr Met Asn Gly Glu Thr Ser Thr Lys Ser Leu Trp Val Ile 320 325 330

Asn Ser Ala Leu Arg Ile Lys Ile Leu Cys Ala Thr Tyr Val Asn 335 340 345 Asn Ser Ala Leu Arg Ile Lys Ile Leu Cys Ala Thr Tyr Val Asn 335 340 345

Val Asn Ile Arg Asp Ile Asp Lys Ile Tyr Val Arg Thr Gly Ile 350 355 360 Val Asn Ile Arg Asp Ile Asp Lys Ile Tyr Val Arg Thr Gly Ile 350 355 360

Tyr His Gly Gly Glu Pro Leu Cys Asp Asn Val Asn Thr Gln Arg 365 370 375 Tyr His Gly Gly Glu Pro Leu Cys Asp Asn Val Asn Thr Gln Arg 365 370 375

Val Pro Cys Ser Asn Pro Arg Trp Asn Glu Trp Leu Asn Tyr Asp 380 385 390 Val Pro Cys Ser Asn Pro Arg Trp Asn Glu Trp Leu Asn Tyr Asp 380 385 390

Ile Tyr Ile Pro Asp Leu Pro Arg Ala Ala Arg Leu Cys Leu Ser 395 400 405 Ile Tyr Ile Pro Asp Leu Pro Arg Wing Wing Arg Leu Cys Leu Ser 395 400 405

Ile Cys Ser Val Lys Gly Arg Lys Gly Ala Lys Glu Glu His Cys Ile Cys Ser Val Lys Gly Arg Lys Gly Ala Lys Glu Glu His Cys

410 415 410 415

Pro Leu Ala Trp Gly Asn Ile Asn Leu Phe Asp Tyr Thr Asp Thr 425 430 435 Pro Leu Wing Trp Gly Asn Ile Asn Leu Phe Asp Tyr Thr Asp Thr 425 430 435

Leu Val Ser Gly Lys Met Ala Leu Asn Leu Trp Pro Val Pro His 440 445 450 Leu Val Ser Gly Lys Met Ala Leu Asn Leu Trp Pro Val Pro His 440 445 450

Gly Leu Glu Asp Leu Leu Asn Pro Ile Gly Val Thr Gly Ser Asn 455 460 465 Gly Leu Glu Asp Leu Leu Asn Pro Ile Gly Val Thr Gly Ser Asn 455 460 465

Pro Asn Lys Glu Thr Pro Cys Leu Glu Leu Glu Phe Asp Trp Phe 470 475 480 Pro Asn Lys Glu Thr Pro Cys Leu Glu Leu Glu Phe Asp Trp Phe 470 475 480

Ser Ser Val Val Lys Phe Pro Asp Met Ser Val Ile Glu Glu His 485 490 495 Ser Ser Val Val Lys Phe Pro Asp Met Ser Val Ile Glu Glu His 485 490 495

Ala Asn Trp Ser Val Ser Arg Glu Ala Gly Phe Ser Tyr Ser His 500 505 510 Wing Asn Trp Ser Val Ser Arg Glu Wing Gly Phe Ser Tyr Ser His 500 505 510

Ala Gly Leu Ser Asn Arg Leu Ala Arg Asp Asn Glu Leu Arg Glu 515 520 525 Ala Gly Leu Ser Asn Arg Leu Ala Arg Asp Asn Glu Leu Arg Glu 515 520 525

Asn Asp Lys Glu Gln Leu Lys Ala Ile Ser Thr Arg Asp Pro Leu 530 535 540 Asn Asp Lys Glu Gln Leu Lys Wing Ile Ser Thr Arg Asp Pro Leu 530 535 540

Ser Glu Ile Thr Glu Gln Glu Lys Asp Phe Leu Trp Ser His Arg 545 550 555 Ser Glu Ile Thr Glu Gln Glu Lys Asp Phe Leu Trp Ser His Arg 545 550 555

His Tyr Cys Val Thr Ile Pro Glu Ile Leu Pro Lys Leu Leu Leu 560 565 570 His Tyr Cys Val Thr Ile Pro Glu Ile Leu Pro Lys Leu Leu Leu 560 565 570

Ser Val Lys Trp Asn Ser Arg Asp Glu Val Ala Gln Met Tyr Cys 575 580 585 Ser Val Lys Trp Asn Ser Arg Asp Glu Val Ala Gln Met Tyr Cys 575 580 585

Leu Val Lys Asp Trp Pro Pro Ile Lys Pro Glu Gln Ala Met Glu 590 595 600 Leu Val Lys Asp Trp Pro Pro Ile Lys Pro Glu Gln Wing Met Glu 590 595 600

Leu Leu Asp Cys Asn Tyr Pro Asp Pro Met Val Arg Gly Phe Ala 605 610 615 Leu Leu Asp Cys Asn Tyr Pro Asp Pro Met Val Arg Gly Phe Ala 605 610 615

Val Arg Cys Leu Glu Lys Tyr Leu Thr Asp Asp Lys Leu Ser Gln 620 625 630 Val Arg Cys Leu Glu Lys Tyr Leu Thr Asp Asp Lys Leu Ser Gln 620 625 630

Tyr Leu Ile Gln Leu Val Gln Val Leu Lys Tyr Glu Gln Tyr Leu 635 640 645 Tyr Leu Ile Gln Leu Val Gln Val Leu Lys Tyr Glu Gln Tyr Leu 635 640 645

Asp Asn Leu Leu Val Arg Phe Leu Leu Lys Lys Ala Leu Thr Asn 650 655 660 Asp Asn Leu Leu Val Arg Phe Leu Leu Lys Lys Ala Leu Thr Asn 650 655 660

Gln Arg Ile Gly His Phe Phe Phe Trp His Leu Lys Ser Glu Met 665 670 675 Gln Arg Ile Gly His Phe Phe Phe Trp His Leu Lys Ser Glu Met 665 670 675

His Asn Lys Thr Val Ser Gln Arg Phe Gly Leu Leu Leu Glu Ser 680 685 690 His Asn Lys Thr Val Ser Gln Arg Phe Gly Leu Leu Leu Glu Ser 680 685 690

Tyr Cys Arg Ala Cys Gly Met Tyr Leu Lys His Leu Asn Arg Gln 695 700 705 Tyr Cys Arg Ala Cys Gly Met Tyr Leu Lys His Leu Asn Arg Gln 695 700 705

Val Glu Ala Met Glu Lys Leu Ile Asn Leu Thr Asp Ile Leu Lys 710 715 720 Val Glu Wing Met Glu Lys Leu Ile Asn Leu Thr Asp Ile Leu Lys 710 715 720

Gln Glu Lys Lys Asp Glu Thr Gln Lys Val Gln Met Lys Phe Leu 725 730 735 Gln Glu Lys Lys Asp Glu Thr Gln Lys Val Gln Met Lys Phe Leu 725 730 735

Val Glu Gln Met Arg Arg Pro Asp Phe Met Asp Ala Leu Gln Gly 740 745 Val Glu Gln Met Arg Arg Pro Asp Phe Met Asp Ala Leu Gln Gly 740 745

Phe Leu Ser Pro Leu Asn Pro Ala His Gln Leu Gly Asn Leu Arg 755 760 765 Phe Leu Ser Pro Leu Asn Pro Ala His Gln Leu Gly Asn Leu Arg 755 760 765

Leu Glu Glu Cys Arg Ile Met Ser Ser Ala Lys Arg Pro Leu Trp 770 775 780 Leu Glu Glu Cys Arg Ile Met Ser Ser Ala Lys Arg Pro Leu Trp 770 775 780

Leu Asn Trp Glu Asn Pro Asp Ile Met Ser Glu Leu Leu Phe Gln 785 790 795 Leu Asn Trp Glu Asn Pro Asp Ile Met Ser Glu Leu Leu Phe Gln 785 790 795

Asn Asn Glu Ile Ile Phe Lys Asn Gly Asp Asp Leu Arg Gln Asp 800 805 810 Asn Asn Glu Ile Ile Phe Lys Asn Gly Asp Asp Leu Arg Gln Asp 800 805 810

Met Leu Thr Leu Gln Ile Ile Arg Ile Met Glu Asn Ile Trp Gln 815 820 825 Met Leu Thr Leu Gln Ile Ile Arg Ile Met Glu Asn Ile Trp Gln 815 820 825

Asn Gln Gly Leu Asp Leu Arg Met Leu Pro Tyr Gly Cys Leu Ser 830 835 840 Asn Gln Gly Leu Asp Leu Arg Met Leu Pro Tyr Gly Cys Leu Ser 830 835 840

Ile Gly Asp Cys Val Gly Leu Ile Glu Val Val Arg Asn Ser His 845 850 855 Ile Gly Asp Cys Val Gly Leu Ile Glu Val Val Arg Asn Ser His 845 850 855

Thr Ile Met Gln Ile Gln Cys Lys Gly Gly Leu Lys Gly Ala Leu 860 865 870 Thr Ile Met Gln Ile Gln Cys Lys Gly Gly Leu Lys Gly Ala Leu 860 865 870

Gln Phe Asn Ser His Thr Leu His Gln Trp Leu Lys Asp Lys Asn 875 880 885 Gln Phe Asn Ser His Thr Leu His Gln Trp Leu Lys Asp Lys Asn 875 880 885

Lys Gly Glu Ile Tyr Asp Ala Ala Ile Asp Leu Phe Thr Arg Ser 890 895 900 Lys Gly Glu Ile Tyr Asp Wing Ile Asp Leu Phe Thr Arg Ser 890 895 900

Cys Ala Gly Tyr Cys Val Ala Thr Phe Ile Leu Gly Ile Gly Asp 905 910 915 Cys Wing Gly Tyr Cys Val Wing Thr Phe Ile Leu Gly Ile Gly Asp 905 910 915

Arg His Asn Ser Asn Ile Met Val Lys Asp Asp Gly Gln Leu Phe 920 925 930 Arg His Asn Ser Asn Ile Met Val Lys Asp Asp Gly Gln Leu Phe 920 925 930

His Ile Asp Phe Gly His Phe Leu Asp His Lys Lys Lys Lys Phe 935 940 945 His Ile Asp Phe Gly His Phe Leu Asp His Lys Lys Lys Lys Phe 935 940 945

Gly Tyr Lys Arg Glu Arg Val Pro Phe Val Leu Thr Gln Asp Phe 950 955 960 Gly Tyr Lys Arg Glu Arg Val Pro Phe Val Leu Thr Gln Asp Phe 950 955 960

Leu Ile Val Ile Ser Lys Gly Ala Gln Glu Cys Thr Lys Thr Arg 965 970 975 Leu Ile Val Ile Ser Lys Gly Ala Gln Glu Cys Thr Lys Thr Arg 965 970 975

Glu Phe Glu Arg Phe Gln Glu Met Cys Tyr Lys Ala Tyr Leu Ala 980 985 990 Glu Phe Glu Arg Phe Gln Glu Met Cys Tyr Lys Ala Tyr Leu Ala 980 985 990

Ile Arg Gln His Ala Asn Leu Phe Ile Asn Leu Phe Ser Met Met 995 1000 1005 Ile Arg Gln His Wing Asn Leu Phe Ile Asn Leu Phe Ser Met Met 995 1000 1005

Leu Gly Ser Gly Met Pro Glu Leu Gln Ser Phe Asp Asp Ile Ala 1010 1015 1020 Leu Gly Ser Gly Met Pro Glu Leu Gln Ser Phe Asp Asp Ile Ala 1010 1015 1020

Tyr Ile Arg Lys Thr Leu Ala Leu Asp Lys Thr Glu Gln Glu Ala 1025 1030 1035 Tyr Ile Arg Lys Thr Leu Ala Leu Asp Lys Thr Glu Gln Glu Ala 1025 1030 1035

Leu Glu Tyr Phe Met Lys Gln Met Asn Asp Ala His His Gly Gly 1040 1045 1050 Leu Glu Tyr Phe Met Lys Gln Met Asn Asp Ala His His Gly Gly 1040 1045 1050

Trp Thr Thr Lys Met Asp Trp Ile Phe His Thr Ile Lys Gln His 1055 1060 1065 Trp Thr Thr Lys Met Asp Trp Ile Phe His Thr Ile Lys Gln His 1055 1060 1065

Ala Leu Asn Ala Leu Asn

<210> 68 <210> 68

<211> 603 <212> PRT <211> 603 <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 68 Met Ser Ala Ala Val Thr Ala Gly Lys Leu Ala Arg Ala Pro Ala 1 5 10 15 <400> 68 Met Ser Wing Wing Val Thr Wing Gly Lys Leu Wing Arg Wing Pro Wing 1 5 10 15

Lys Glu Val Phe Ala Gly Lys Ile Val Pro Lys Ser Leu Leu Leu 80 85 90 Lys Glu Val Phe Wing Gly Lys Ile Val Pro Lys Ser Leu Leu Leu 80 85 90

Lys Pro His Gln Arg Glu Lys Met Ser Met Glu Ile Ser Ile His 95 100 105 Lys Pro His Gln Arg Glu Lys Met Ser Met Glu Ile Ser Ile His 95 100 105

Ile Thr Cys Leu Thr Ile Pro Pro Arg Phe Ser Ile Ala Pro Ser Ile Thr Cys Leu Thr Ile Pro Pro Arg Phe Ser Ile Ala Pro Ser

320 325 330 320 325 330

Tyr Gly Leu Gly Tyr Gln Leu Cys Asp Asn Ser Val Gly Val Leu 425 430 435 Tyr Gly Leu Gly Tyr Gln Leu Cys Asp Asn Ser Val Gly Val Leu 425 430 435

Lys Ala Ser Lys Ala Ser

<210> 69 <210> 69

<211> 1447 <211> 1447

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 69 Met Ala Ser Ala Gly Asn Ala Ala Glu Pro Gln Asp Arg Gly Gly 1 5 10 15 <400> 69 Met Wing Ser Wing Gly Asn Wing Gl Glu Pro Gln Asp Arg Gly Gly 1 5 10 15

Gly Gly Ser Gly Cys Ile Gly Ala Pro Gly Arg Pro Ala Gly Gly 20 25 Gly Gly Ser Gly Cys Ile Gly Ala Pro Gly Arg Pro Ala Gly Gly 20 25

Gly Arg Arg Arg Arg Thr Gly Gly Leu Arg Arg Ala Ala Ala Pro 35 40 45 Gly Arg Arg Arg Arg Thr Gly Gly Leu Arg Arg Wing Wing Wing Pro 35 40 45

Asp Arg Asp Tyr Leu His Arg Pro Ser Tyr Cys Asp Ala Ala Phe 50 55 60 Asp Arg Asp Tyr Leu His Arg Pro Ser Tyr Cys Asp Ala Ala Phe 50 55 60

Ala Leu Glu Gln Ile Ser Lys Gly Lys Ala Thr Gly Arg Lys Ala 65 70 75 Wing Leu Glu Gln Ile Ser Lys Gly Lys Wing Thr Gly Arg Lys Wing 65 70 75

Pro Leu Trp Leu Arg Ala Lys Phe Gln Arg Leu Leu Phe Lys Leu 80 85 90 Pro Leu Trp Leu Arg Ala Lys Phe Gln Arg Leu Leu Phe Lys Leu 80 85 90

Gly Cys Tyr Ile Gln Lys Asn Cys Gly Lys Phe Leu Val Val Gly 95 100 105 Gly Cys Tyr Ile Gln Lys Asn Cys Gly Lys Phe Leu Val Val Gly 95 100 105

Leu Leu Ile Phe Gly Ala Phe Ala Val Gly Leu Lys Ala Ala Asn 110 115 120 Leu Leu Ile Phe Gly Wing Phe Wing Val Gly Leu Lys Wing Wing Asn 110 115 120

Leu Glu Thr Asn Val Glu Glu Leu Trp Val Glu Val Gly Gly Arg 125 130 135 Leu Glu Thr Asn Val Glu Glu Leu Trp Val Glu Val Gly Gly Arg 125 130 135

Val Ser Arg Glu Leu Asn Tyr Thr Arg Gln Lys Ile Gly Glu Glu 140 145 150 Val Ser Arg Glu Leu Asn Tyr Thr Arg Gln Lys Ile Gly Glu Glu 140 145 150

Ala Met Phe Asn Pro Gln Leu Met Ile Gln Thr Pro Lys Glu Glu 155 160 165 Wing Met Phe Asn Pro Gln Leu Met Ile Gln Thr Pro Lys Glu Glu 155 160 165

Gly Ala Asn Val Leu Thr Thr Glu Ala Leu Leu Gln His Leu Asp 170 175 180 Gly Ala Asn Val Leu Thr Thr Glu Ala Leu Leu Gln His Leu Asp 170 175 180

Ser Ala Leu Gln Ala Ser Arg Val His Val Tyr Met Tyr Asn Arg 185 190 195 Ser Ala Leu Gln Ala Ser Arg Val His Val Tyr Met Tyr Asn Arg 185 190 195

Gln Trp Lys Leu Glu His Leu Cys Tyr Lys Ser Gly Glu Leu Ile 200 205 210 Gln Trp Lys Leu Glu His Leu Cys Tyr Lys Ser Gly Glu Leu Ile 200 205 210

Thr Glu Thr Gly Tyr Met Asp Gln Ile Ile Glu Tyr Leu Tyr Pro 215 220 225 Thr Glu Thr Gly Tyr Met Asp Gln Ile Ile Glu Tyr Leu Tyr Pro 215 220 225

Cys Leu Ile Ile Thr Pro Leu Asp Cys Phe Trp Glu Gly Ala Lys 230 235 240 Cys Leu Ile Ile Thr Pro Leu Asp Cys Phe Trp Glu Gly Ala Lys 230 235 240

Leu Gln Ser Gly Thr Ala Tyr Leu Leu Gly Lys Pro Pro Leu Arg 245 250 255 Leu Gln Ser Gly Thr Wing Tyr Leu Leu Gly Lys Pro Pro Leu Arg 245 250 255

Trp Thr Asn Phe Asp Pro Leu Glu Phe Leu Glu Glu Leu Lys Lys 260 265 270 Trp Thr Asn Phe Asp Pro Leu Glu Phe Leu Glu Glu Leu Lys Lys 260 265 270

Ile Asn Tyr Gln Val Asp Ser Trp Glu Glu Met Leu Asn Lys Ala 275 280 285 Ile Asn Tyr Gln Val Asp Ser Trp Glu Glu Met Leu Asn Lys Ala 275 280 285

Glu Val Gly His Gly Tyr Met Asp Arg Pro Cys Leu Asn Pro Ala 290 295 300 Glu Val Gly His Gly Tyr Met Asp Arg Pro Cys Leu Asn Pro Wing 290 295 300

Asp Pro Asp Cys Pro Ala Thr Ala Pro Asn Lys Asn Ser Thr Lys 305 310 315 Asp Pro Asp Cys Pro Wing Thr Wing Pro Asn Lys Asn Ser Thr Lys 305 310 315

Pro Leu Asp Met Ala Leu Val Leu Asn Gly Gly Cys His Gly Leu 320 325 330 Pro Leu Asp Met Ala Leu Val Leu Asn Gly Gly Cys His Gly Leu 320 325 330

Ser Arg Lys Tyr Met His Trp Gln Glu Glu Leu Ile Val Gly Gly 335 340 345 Ser Arg Lys Tyr Met His Trp Gln Glu Glu Leu Ile Val Gly Gly 335 340 345

Thr Val Lys Asn Ser Thr Gly Lys Leu Val Ser Ala His Ala Leu 350 355 Thr Val Lys Asn Ser Thr Gly Lys Leu Val Ser Ala His Ala Leu 350 355

Gln Thr Met Phe Gln Leu Met Thr Pro Lys Gln Met Tyr Glu His 365 370 Gln Thr Met Phe Gln Leu Met Thr Pro Lys Gln Met Tyr Glu His 365 370

Phe Lys Gly Tyr Glu Tyr Val Ser His Ile Asn Trp Asn Glu Asp 380 385 390 Phe Lys Gly Tyr Glu Tyr Val Ser His Ile Asn Trp Asn Glu Asp 380 385 390

Lys Ala Ala Ala Ile Leu Glu Ala Trp Gln Arg Thr Tyr Val Glu 395 400 405 Lys Wing Wing Ile Leu Glu Wing Trp Gln Arg Thr Tyr Val Glu 395 400 405

Val Val His Gln Ser Val Ala Gln Asn Ser Thr Gln Lys Val Leu 410 415 420 Val Val His Gln Ser Val Ala Gln Asn Ser Thr Gln Lys Val Leu 410 415 420

Ser Phe Thr Thr Thr Thr Leu Asp Asp Ile Leu Lys Ser Phe Ser 425 430 435 Ser Phe Thr Thr Thr Thr Leu Asp Asp Ile Leu Lys Ser Phe Ser 425 430 435

Asp Val Ser Val Ile Arg Val Ala Ser Gly Tyr Leu Leu Met Leu 440 445 450 Asp Val Ser Val Ile Arg Val Ala Ser Gly Tyr Leu Leu Met Leu 440 445 450

Ala Tyr Ala Cys Leu Thr Met Leu Arg Trp Asp Cys Ser Lys Ser 455 460 465 Wing Tyr Wing Cys Leu Thr Met Leu Arg Trp Asp Cys Ser Lys Ser 455 460 465

Gln Gly Ala Val Gly Leu Ala Gly Val Leu Leu Val Ala Leu Ser 470 475 480 Gln Gly Wing Val Gly Leu Wing Gly Val Leu Leu Val Wing Leu Ser 470 475 480

Val Ala Ala Gly Leu Gly Leu Cys Ser Leu Ile Gly Ile Ser Phe 485 490 495 Wing Val Wing Gly Leu Gly Leu Cys Ser Leu Ile Gly Ile Ser Phe 485 490 495

Asn Ala Ala Thr Thr Gln Val Leu Pro Phe Leu Ala Leu Gly Val 500 505 510 Asn Wing Wing Thr Thr Gln Val Leu Pro Phe Leu Wing Leu Gly Val 500 505 510

Gly Val Asp Asp Val Phe Leu Leu Ala His Ala Phe Ser Glu Thr 515 520 525 Gly Val Asp Asp Val Phe Leu Leu Wing His Wing Phe Ser Glu Thr 515 520 525

Gly Gln Asn Lys Arg Ile Pro Phe Glu Asp Arg Thr Gly Glu Cys 530 535 540 Gly Gln Asn Lys Arg Ile Pro Phe Glu Asp Arg Thr Gly Glu Cys 530 535 540

Leu Lys Arg Thr Gly Ala Ser Val Ala Leu Thr Ser Ile Ser Asn 545 550 555 Leu Lys Arg Thr Gly Ala Ser Val Ala Leu Thr Ser Ile Ser Asn 545 550 555

Val Thr Ala Phe Phe Met Ala Ala Leu Ile Pro Ile Pro Ala Leu 560 565 570 Val Thr Wing Phe Phe Met Wing Wing Leu Ile Pro Ile Pro Wing Leu 560 565 570

Arg Ala Phe Ser Leu Gln Ala Ala Val Val Val Val Phe Asn Phe 575 580 585 Arg Wing Phe Ser Leu Gln Wing Wing Val Val Val Val Phe Asn Phe 575 580 585

Ala Met Val Leu Leu Ile Phe Pro Ala Ile Leu Ser Met Asp Leu 590 595 600 Wing Met Val Leu Leu Ile Phe Pro Wing Ile Leu Ser Met Asp Leu 590 595 600

Tyr Arg Arg Glu Asp Arg Arg Leu Asp Ile Phe Cys Cys Phe Thr 605 610 615 Tyr Arg Arg Glu Asp Arg Arg Leu Asp Ile Phe Cys Cys Phe Thr 605 610 615

Ser Pro Cys Val Ser Arg Val Ile Gln Val Glu Pro Gln Ala Tyr 620 625 630 Ser Pro Cys Val Ser Arg Val Ile Gln Val Glu Pro Gln Ala Tyr 620 625 630

Thr Asp Thr His Asp Asn Thr Arg Tyr Ser Pro Pro Pro Pro Tyr 635 640 645 Thr Asp Thr His Asp Asn Thr Arg Tyr Ser Pro Pro Pro Pro Tyr 635 640 645

Ser Ser His Ser Phe Ala His Glu Thr Gln Ile Thr Met Gln Ser 650 655 660 Ser Ser His Ser Phe Ala His Glu Thr Gln Ile Thr Met Gln Ser 650 655 660

Thr Val Gln Leu Arg Thr Glu Tyr Asp Pro His Thr His Val Tyr 665 670 675 Thr Val Gln Leu Arg Thr Glu Tyr Asp Pro His Thr His Val Tyr 665 670 675

Tyr Thr Thr Ala Glu Pro Arg Ser Glu Ile Ser Val Gln Pro Val 680 685 690 Tyr Thr Thr Wing Glu Pro Arg Ser Glu Ile Ser Val Gln Pro Val 680 685 690

Thr Val Thr Gln Asp Thr Leu Ser Cys Gln Ser Pro Glu Ser Thr Thr Val Thr Gln Asp Thr Leu Ser Cys Gln Ser Pro Glu Ser Thr

695 700 695 700

Ser Ser Thr Arg Asp Leu Leu Ser Gln Phe Ser Asp Ser Ser Leu 710 715 720 Be Be Thr Arg Asp Leu Leu Be Gln Phe Be Asp Be Be Leu 710 715 720

His Cys Leu Glu Pro Pro Cys Thr Lys Trp Thr Leu Ser Ser Phe 725 730 735 His Cys Leu Glu Pro Pro Cys Thr Lys Trp Thr Leu Ser Ser Phe 725 730 735

Ala Glu Lys His Tyr Ala Pro Phe Leu Leu Lys Pro Lys Ala Lys 740 745 750 Wing Glu Lys His Tyr Wing Pro Phe Leu Leu Lys Pro Lys Wing Lys 740 745 750

Val Val Val Ile Phe Leu Phe Leu Gly Leu Leu Gly Val Ser Leu 755 760 765 Val Val Val Ile Phe Leu Phe Leu Gly Leu Leu Gly Val Ser Leu 755 760 765

Tyr Gly Thr Thr Arg Val Arg Asp Gly Leu Asp Leu Thr Asp Ile 770 775 780 Tyr Gly Thr Thr Arg Val Arg Asp Gly Leu Asp Leu Thr Asp Ile 770 775 780

Val Pro Arg Glu Thr Arg Glu Tyr Asp Phe Ile Ala Ala Gln Phe 785 790 795 Val Pro Arg Glu Thr Arg Glu Tyr Asp Phe Ile Wing Gln Phe 785 790 795

Lys Tyr Phe Ser Phe Tyr Asn Met Tyr Ile Val Thr Gln Lys Ala 800 805 810 Lys Tyr Phe Ser Phe Tyr Asn Met Tyr Ile Val Thr Gln Lys Wing 800 805 810

Asp Tyr Pro Asn Ile Gln His Leu Leu Tyr Asp Leu His Arg Ser 815 820 825 Asp Tyr Pro Asn Ile Gln His Leu Leu Tyr Asp Leu His Arg Ser 815 820 825

Phe Ser Asn Val Lys Tyr Val Met Leu Glu Glu Asn Lys Gln Leu 830 835 840 Phe Ser Asn Val Lys Tyr Val Met Leu Glu Glu Asn Lys Gln Leu 830 835 840

Pro Lys Met Trp Leu His Tyr Phe Arg Asp Trp Leu Gln Gly Leu 845 850 855 Pro Lys Met Trp Leu His Tyr Phe Arg Asp Trp Leu Gln Gly Leu 845 850 855

Gln Asp Ala Phe Asp Ser Asp Trp Glu Thr Gly Lys Ile Met Pro 860 865 870 Gln Asp Wing Phe Asp Ser Asp Trp Glu Thr Gly Lys Ile Met Pro 860 865 870

Asn Asn Tyr Lys Asn Gly Ser Asp Asp Gly Val Leu Ala Tyr Lys 875 880 885 Asn Asn Tyr Lys Asn Gly Ser Asp Asp Gly Val Leu Wing Tyr Lys 875 880 885

Leu Leu Val Gln Thr Gly Ser Arg Asp Lys Pro Ile Asp Ile Ser 890 895 900 Leu Leu Val Gln Thr Gly Ser Arg Asp Lys Pro Ile Asp Ile Ser 890 895 900

Gln Leu Thr Lys Gln Arg Leu Val Asp Ala Asp Gly Ile Ile Asn 905 910 915 Gln Leu Thr Lys Gln Arg Leu Val Asp Wing Asp Gly Ile Ile Asn 905 910 915

Pro Ser Ala Phe Tyr Ile Tyr Leu Thr Ala Trp Val Ser Asn Asp 920 925 930 Pro Ser Wing Phe Tyr Ile Tyr Leu Thr Wing Trp Val Ser Asn Asp 920 925 930

Pro Val Ala Tyr Ala Ala Ser Gln Ala Asn Ile Arg Pro His Arg 935 940 945 Pro Val Ala Tyr Ala Ala Ser Gln Ala Asn Ile Arg Pro His Arg 935 940 945

Pro Glu Trp Val His Asp Lys Ala Asp Tyr Met Pro Glu Thr Arg 950 955 960 Pro Glu Trp Val His Asp Lys Wing Asp Tyr Met Pro Glu Thr Arg 950 955 960

Leu Arg Ile Pro Ala Ala Glu Pro Ile Glu Tyr Ala Gln Phe Pro 965 970 975 Leu Arg Ile Pro Wing Glu Pro Ile Glu Tyr Wing Gln Phe Pro 965 970 975

Phe Tyr Leu Asn Gly Leu Arg Asp Thr Ser Asp Phe Val Glu Ala 980 985 990 Phe Tyr Leu Asn Gly Leu Arg Asp Thr Ser Asp Phe Val Glu Ala 980 985 990

Ile Glu Lys Val Arg Thr Ile Cys Ser Asn Tyr Thr Ser Leu Gly 995 1000 1005 Ile Glu Lys Val Arg Thr Ile Cys Ser Asn Tyr Thr Ser Leu Gly 995 1000 1005

Leu Ser Ser Tyr Pro Asn Gly Tyr Pro Phe Leu Phe Trp Glu Gln 1010 1015 1020 Leu Ser Ser Tyr Pro Asn Gly Tyr Pro Phe Leu Phe Trp Glu Gln 1010 1015 1020

Tyr Ile Gly Leu Arg His Trp Leu Leu Leu Phe Ile Ser Val Val 1025 1030 1035 Leu Ala Cys Thr Phe Leu Val Cys Ala Val Phe Leu Leu Asn Pro 1040 1045 1050 Tyr Ile Gly Leu Arg His Trp Leu Leu Leu Phe Ile Ser Val Val 1025 1030 1035 Leu Ala Cys Thr Phe Leu Val Cys Ala Val Phe Leu Leu Asn Pro 1040 1045 1050

Trp Thr Ala Gly Ile Ile Val Met Val Leu Ala Leu Met Thr Val 1055 1060 1065 Trp Thr Wing Gly Ile Ile Val Met Val Leu Wing Leu Met Thr Val 1055 1060 1065

Glu Leu Phe Gly Met Met Gly Leu Ile Gly Ile Lys Leu Ser Ala 1070 1075 1080 Glu Leu Phe Gly Met Met Gly Leu Ile Gly Ile Lys Leu Ser Ala 1070 1075 1080

Val Pro Val Val Ile Leu Ile Ala Ser Val Gly Ile Gly Val Glu 1085 1090 1095 Val Pro Val Val Ile Leu Ile Ala Ser Val Gly Ile Gly Val Glu 1085 1090 1095

Phe Thr Val His Val Ala Leu Ala Phe Leu Thr Ala Ile Gly Asp 1100 1105 1110 Phe Thr Val His Val Wing Leu Wing Phe Leu Thr Wing Ile Gly Asp 1100 1105 1110

Lys Asn Arg Arg Ala Val Leu Ala Leu Glu His Met Phe Ala Pro 1115 1120 1125 Lys Asn Arg Arg Ala Val Leu Ala Leu Glu His Met Phe Ala Pro 1115 1120 1125

Val Leu Asp Gly Ala Val Ser Thr Leu Leu Gly Val Leu Met Leu 1130 1135 1140 Val Leu Asp Gly Ala Val Ser Thr Leu Leu Gly Val Leu Met Leu 1130 1135 1140

Ala Gly Ser Glu Phe Asp Phe Ile Val Arg Tyr Phe Phe Ala Val 1145 1150 1155 Ala Gly Ser Glu Phe Asp Phe Ile Val Arg Tyr Phe Phe Ala Val 1145 1150 1155

Leu Ala Ile Leu Thr Ile Leu Gly Val Leu Asn Gly Leu Val Leu 1160 1165 1170 Leu Wing Ile Leu Thr Ile Leu Gly Val Leu Asn Gly Leu Val Leu 1160 1165 1170

Leu Pro Val Leu Leu Ser Phe Phe Gly Pro Tyr Pro Glu Val Ser 1175 1180 1185 Leu Pro Val Leu Leu Ser Phe Phe Gly Pro Tyr Pro Glu Val Ser 1175 1180 1185

Pro Ala Asn Gly Leu Asn Arg Leu Pro Thr Pro Ser Pro Glu Pro 1190 1195 1200 Pro Wing Asn Gly Leu Asn Arg Leu Pro Thr Pro Ser Pro Glu Pro 1190 1195 1200

Pro Pro Ser Val Val Arg Phe Ala Met Pro Pro Gly His Thr His 1205 1210 1215 Pro Pro Ser Val Val Arg Phe Wing Met Pro Pro Gly His Thr His 1205 1210 1215

Ser Gly Ser Asp Ser Ser Asp Ser Glu Tyr Ser Ser Gln Thr Thr 1220 1225 1230 Be Gly Be Asp Be Be Asp Be Glu Tyr Be Be Gln Thr Thr 1220 1225 1230

Val Ser Gly Leu Ser Glu Glu Leu Arg His Tyr Glu Ala Gln Gln 1235 1240 1245 Val Ser Gly Leu Ser Glu Glu Leu Arg His Tyr Glu Ala Gln Gln 1235 1240 1245

Gly Ala Gly Gly Pro Ala His Gln Val Ile Val Glu Ala Thr Glu 1250 1255 1260 Gly Wing Gly Gly Pro Wing His Gln Val Ile Val Glu Wing Thr Glu 1250 1255 1260

Asn Pro Val Phe Ala His Ser Thr Val Val His Pro Glu Ser Arg 1265 1270 1275 Asn Pro Val Phe Ala His Ser Thr Val Val His Pro Glu Ser Arg 1265 1270 1275

His His Pro Pro Ser Asn Pro Arg Gln Gln Pro His Leu Asp Ser 1280 1285 1290 His His Pro Pro Ser Asn Pro Arg Gln Gln Pro His Leu Asp Ser 1280 1285 1290

Gly Ser Leu Pro Pro Gly Arg Gln Gly Gln Gln Pro Arg Arg Asp 1295 1300 1305 Gly Ser Leu Pro Pro Gly Arg Gln Gly Gln Gln Pro Arg Arg Asp 1295 1300 1305

Pro Pro Arg Glu Gly Leu Trp Pro Pro Leu Tyr Arg Pro Arg Arg 1310 1315 1320 Pro Pro Arg Glu Gly Leu Trp Pro Pro Leu Tyr Arg Pro Arg Arg 1310 1315 1320

Asp Ala Phe Glu Ile Ser Thr Glu Gly His Ser Gly Pro Ser Asn 1325 1330 1335 Asp Wing Phe Glu Ile Ser Thr Glu Gly His Ser Gly Pro Ser Asn 1325 1330 1335

Arg Ala Arg Trp Gly Pro Arg Gly Ala Arg Ser His Asn Pro Arg 1340 1345 1350 Arg Ala Arg Trp Gly Pro Arg Gly Ala Arg Ser His Asn Pro Arg 1340 1345 1350

Asn Pro Ala Ser Thr Ala Met Gly Ser Ser Val Pro Gly Tyr Cys 1355 1360 1365 Asn Pro Wing Ser Thr Wing Met Gly Ser Ser Val Pro Gly Tyr Cys 1355 1360 1365

Gln Pro Ile Thr Thr Val Thr Ala Ser Ala Ser Val Thr Val Ala 1370 1375 1380 Gln Pro Ile Thr Thr Val Thr Ala Ser Ala Ser Val Thr Val Ala 1370 1375 1380

Val His Pro Pro Pro Val Pro Gly Pro Gly Arg Asn Pro Arg Gly 1385 1390 1395 Val His Pro Pro Pro Val Pro Gly Pro Gly Arg Asn Pro Arg Gly 1385 1390 1395

Gly Leu Cys Pro Gly Tyr Pro Glu Thr Asp His Gly Leu Phe Glu 1400 1405 1410 Gly Leu Cys Pro Gly Tyr Pro Glu Thr Asp His Gly Leu Phe Glu 1400 1405 1410

Asp Pro His Val Pro Phe His Val Arg Cys Glu Arg Arg Asp Ser 1415 1420 1425 Asp Pro His Val Pro Phe His Val Arg Cys Glu Arg Arg Asp Ser 1415 1420 1425

Lys Val Glu Val Ile Glu Leu Gln Asp Val Glu Cys Glu Glu Arg 1430 1435 1440 Lys Val Glu Val Ile Glu Leu Gln Asp Val Glu Cys Glu Glu Arg 1430 1435 1440

Pro Arg Gly Ser Ser Ser Asn 1445 Pro Arg Gly Be Be Be Asn 1445

<210> 70 <210> 70

<211> 928 <211> 928

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 70 Met Pro Pro Lys Thr Pro Arg Lys Thr Ala Ala Thr Ala Ala Ala 1 5 10 15 <400> 70 Met Pro Pro Lys Thr Pro Arg Lys Thr Wing Thr Wing Wing Wing 1 5 10 15

Ala Ala Ala Glu Pro Pro Ala Pro Pro Pro Pro Pro Pro Pro Glu 20 25 30 Wing Wing Glu Pro Wing Pro Wing Pro Pro Pro Pro Pro Pro Glu 20 25 30

Glu Asp Pro Glu Gln Asp Ser Gly Pro Glu Asp Leu Pro Leu Val 35 40 45 Glu Asp Pro Glu Gln Asp Ser Gly Pro Glu Asp Leu Pro Leu Val 35 40 45

Arg Leu Glu Phe Glu Glu Thr Glu Glu Pro Asp Phe Thr Ala Leu 50 55 60 Arg Leu Glu Phe Glu Glu Thr Glu Glu Pro Asp Phe Thr Ala Leu 50 55 60

Cys Gln Lys Leu Lys Ile Pro Asp His Val Arg Glu Arg Ala Trp 65 70 75 Cys Gln Lys Leu Lys Ile Pro Asp His Val Arg Glu Arg Wing Trp 65 70 75

Leu Thr Trp Glu Lys Val Ser Ser Val Asp Gly Val Leu Gly Gly 80 85 90 Leu Thr Trp Glu Lys Val Ser Ser Val Asp Gly Val Leu Gly Gly 80 85 90

Tyr Ile Gln Lys Lys Lys Glu Leu Trp Gly Ile Cys Ile Phe Ile 95 100 105 Tyr Ile Gln Lys Lys Lys Glu Leu Trp Gly Ile Cys Ile Phe Ile 95 100 105

Ala Arg Val Asp Leu Asp Glu Met Ser Phe Thr Leu Leu Ser Tyr 110 115 120 Wing Arg Val Asp Leu Asp Glu Met Ser Phe Thr Leu Leu Ser Tyr 110 115 120

Arg Lys Thr Tyr Glu Ile Ser Val His Lys Phe Phe Asn Leu Leu 125 130 135 Arg Lys Thr Tyr Glu Ile Ser Val His Lys Phe Phe Asn Leu Leu 125 130 135

Lys Glu Ile Asp Thr Ser Thr Lys Val Asp Asn Ala Met Ser Arg 140 145 150 Lys Glu Ile Asp Thr Ser Thr Lys Val Asp Asn Wing Met Ser Arg 140 145 150

Leu Leu Lys Lys Tyr Asp Val Leu Phe Ala Leu Phe Ser Lys Leu 155 160 165 Leu Leu Lys Lys Tyr Asp Val Leu Phe Ala Leu Phe Ser Lys Leu 155 160 165

Glu Arg Thr Cys Glu Leu Ile Tyr Leu Thr Gln Pro Ser Ser Ser 170 175 180 Glu Arg Thr Cys Glu Leu Ile Tyr Leu Thr Gln Pro Ser Ser Ser 170 175 180

Ile Ser Thr Glu Ile Asn Ser Ala Leu Val Leu Lys Val Ser Trp 185 190 195 Ile Ser Thr Glu Ile Asn Ser Ala Leu Val Leu Lys Val Ser Trp 185 190 195

Ile Thr Phe Leu Leu Ala Lys Gly Glu Val Leu Gln Met Glu Asp 200 205 210 Ile Thr Phe Leu Leu Ala Lys Gly Glu Val Leu Gln Met Glu Asp 200 205 210

Asp Leu Val Ile Ser Phe Gln Leu Met Leu Cys Val Leu Asp Tyr 215 220 225 Asp Leu Val Ile Ser Phe Gln Leu Met Leu Cys Val Leu Asp Tyr 215 220 225

Phe Ile Lys Leu Ser Pro Pro Met Leu Leu Lys Glu Pro Tyr Lys Phe Ile Lys Leu Ser Pro Pro Met Leu Leu Lys Glu Pro Tyr Lys

230 235 230 235

Thr Ala Val Ile Pro Ile Asn Gly Ser Pro Arg Thr Pro Arg Arg 245 250 255 Thr Wing Val Ile Pro Ile Asn Gly Ser Pro Arg Thr Pro Arg Arg 245 250 255

Gly Gln Asn Arg Ser Ala Arg Ile Ala Lys Gln Leu Glu Asn Asp 260 265 270 Gly Gln Asn Arg Ser Ala Arg Ile Ala Lys Gln Leu Glu Asn Asp 260 265 270

Thr Arg Ile Ile Glu Val Leu Cys Lys Glu His Glu Cys Asn Ile 275 280 285 Thr Arg Ile Ile Glu Val Leu Cys Lys Glu His Glu Cys Asn Ile 275 280 285

Asp Glu Val Lys Asn Val Tyr Phe Lys Asn Phe Ile Pro Phe Met 290 295 300 Asp Glu Val Lys Asn Val Tyr Phe Lys Asn Phe Ile Pro Phe Met 290 295 300

Asn Ser Leu Gly Leu Val Thr Ser Asn Gly Leu Pro Glu Val Glu 305 310 315 Asn Ser Leu Gly Leu Val Thr Ser Asn Gly Leu Pro Glu Val Glu 305 310 315

Asn Leu Ser Lys Arg Tyr Glu Glu Ile Tyr Leu Lys Asn Lys Asp 320 325 330 Asn Leu Ser Lys Arg Tyr Glu Glu Ile Tyr Leu Lys Asn Lys Asp 320 325 330

Leu Asp Arg Arg Leu Phe Leu Asp His Asp Lys Thr Leu Gln Thr 335 340 345 Leu Asp Arg Arg Leu Phe Leu Asp His Asp Lys Thr Leu Gln Thr 335 340 345

Asp Ser Ile Asp Ser Phe Glu Thr Gln Arg Thr Pro Arg Lys Ser 350 355 360 Asp Ser Ile Asp Ser Phe Glu Thr Gln Arg Thr Pro Arg Lys Ser 350 355 360

Asn Leu Asp Glu Glu Val Asn Ile Ile Pro Pro His Thr Pro Val 365 370 375 Asn Leu Asp Glu Glu Val Asn Ile Ile Pro Pro His Thr Pro Val 365 370 375

Arg Thr Val Met Asn Thr Ile Gln Gln Leu Met Met Ile Leu Asn 380 385 390 Arg Thr Val Met Asn Thr Ile Gln Gln Leu Met Met Ile Leu Asn 380 385 390

Ser Ala Ser Asp Gln Pro Ser Glu Asn Leu Ile Ser Tyr Phe Asn 395 400 405 Be Wing Be Asp Gln Pro Be Glu Asn Leu Ile Be Tyr Phe Asn 395 400 405

Asn Cys Thr Val Asn Pro Lys Glu Ser Ile Leu Lys Arg Val Lys 410 415 420 Asn Cys Thr Val Asn Pro Lys Glu Ser Ile Leu Lys Arg Val Lys 410 415 420

Asp Ile Gly Tyr Ile Phe Lys Glu Lys Phe Ala Lys Ala Val Gly 425 430 435 Asp Ile Gly Tyr Ile Phe Lys Glu Lys Phe Ala Lys Ala Val Gly 425 430 435

Gln Gly Cys Val Glu Ile Gly Ser Gln Arg Tyr Lys Leu Gly Val 440 445 450 Gln Gly Cys Val Glu Ile Gly Ser Gln Arg Tyr Lys Leu Gly Val 440 445 450

Arg Leu Tyr Tyr Arg Val Met Glu Ser Met Leu Lys Ser Glu Glu 455 460 465 Arg Leu Tyr Tyr Arg Val Met Glu Ser Met Leu Lys Ser Glu Glu 455 460 465

Glu Arg Leu Ser Ile Gln Asn Phe Ser Lys Leu Leu Asn Asp Asn 470 475 480 Glu Arg Leu Ser Ile Gln Asn Phe Ser Lys Leu Leu Asn Asp Asn 470 475 480

Ile Phe His Met Ser Leu Leu Ala Cys Ala Leu Glu Val Val Met 485 490 495 Ile Phe His Met Ser Leu Leu Ala Cys Ala Leu Glu Val Val Met 485 490 495

Ala Thr Tyr Ser Arg Ser Thr Ser Gln Asn Leu Asp Ser Gly Thr 500 505 510 Wing Thr Tyr Ser Arg Ser Thr Ser Gln Asn Leu Asp Ser Gly Thr 500 505 510

Asp Leu Ser Phe Pro Trp Ile Leu Asn Val Leu Asn Leu Lys Ala 515 520 525 Asp Leu Ser Phe Pro Trp Ile Leu Asn Val Leu Asn Leu Lys Ala 515 520 525

Phe Asp Phe Tyr Lys Val Ile Glu Ser Phe Ile Lys Ala Glu Gly 530 535 540 Phe Asp Phe Tyr Lys Val Ile Glu Ser Phe Ile Lys Ala Glu Gly 530 535 540

Asn Leu Thr Arg Glu Met Ile Lys His Leu Glu Arg Cys Glu His 545 550 555 Asn Leu Thr Arg Glu Met Ile Lys His Leu Glu Arg Cys Glu His 545 550 555

Arg Ile Met Glu Ser Leu Ala Trp Leu Ser Asp Ser Pro Leu Phe 560 565 Arg Ile Met Glu Ser Leu Wing Trp Leu Ser Asp Ser Pro Leu Phe 560 565

Asp Leu Ile Lys Gln Ser Lys Asp Arg Glu Gly Pro Thr Asp His 575 580 Asp Leu Ile Lys Gln Ser Lys Asp Arg Glu Gly Pro Thr Asp His 575 580

Leu Glu Ser Ala Cys Pro Leu Asn Leu Pro Leu Gln Asn Asn His 590 595 600 Leu Glu Ser Ala Cys Pro Leu Asn Leu Pro Leu Gln Asn Asn His 590 595 600

Thr Ala Ala Asp Met Tyr Leu Ser Pro Val Arg Ser Pro Lys Lys 605 610 615 Thr Wing Wing Asp Met Tyr Leu Ser Pro Val Arg Ser Pro Lys Lys 605 610 615

Lys Gly Ser Thr Thr Arg Val Asn Ser Thr Ala Asn Ala Glu Thr 620 625 630 Lys Gly Ser Thr Thr Arg Val Asn Ser Thr Wing Asn Wing Glu Thr 620 625 630

Gln Ala Thr Ser Ala Phe Gln Thr Gln Lys Pro Leu Lys Ser Thr 635 640 645 Gln Wing Thr Ser Wing Phe Gln Thr Gln Lys Pro Leu Lys Ser Thr 635 640 645

Ser Leu Ser Leu Phe Tyr Lys Lys Val Tyr Arg Leu Ala Tyr Leu 650 655 660 Ser Leu Ser Leu Phe Tyr Lys Lys Val Tyr Arg Leu Ala Tyr Leu 650 655 660

Arg Leu Asn Thr Leu Cys Glu Arg Leu Leu Ser Glu His Pro Glu 665 670 675 Arg Leu Asn Thr Leu Cys Glu Arg Leu Leu Ser Glu His Pro Glu 665 670 675

Leu Glu His Ile Ile Trp Thr Leu Phe Gln His Thr Leu Gln Asn 680 685 690 Leu Glu His Ile Ile Trp Thr Leu Phe Gln His Thr Leu Gln Asn 680 685 690

Glu Tyr Glu Leu Met Arg Asp Arg His Leu Asp Gln Ile Met Met 695 700 705 Glu Tyr Glu Leu Met Arg Asp Arg His Leu Asp Gln Ile Met Met 695 700 705

Cys Ser Met Tyr Gly Ile Cys Lys Val Lys Asn Ile Asp Leu Lys 710 715 720 Cys Ser Met Tyr Gly Ile Cys Lys Val Lys Asn Ile Asp Leu Lys 710 715 720

Phe Lys Ile Ile Val Thr Ala Tyr Lys Asp Leu Pro His Ala Val 725 730 735 Phe Lys Ile Ile Val Thr Ala Tyr Lys Asp Leu Pro His Ala Val 725 730 735

Gln Glu Thr Phe Lys Arg Val Leu Ile Lys Glu Glu Glu Tyr Asp 740 745 750 Gln Glu Thr Phe Lys Arg Val Leu Ile Lys Glu Glu Glu Tyr Asp 740 745 750

Ser Ile Ile Val Phe Tyr Asn Ser Val Phe Met Gln Arg Leu Lys 755 760 765 Ser Ile Ile Val Phe Tyr Asn Ser Val Phe Met Gln Arg Leu Lys 755 760 765

Thr Asn Ile Leu Gln Tyr Ala Ser Thr Arg Pro Pro Thr Leu Ser 770 775 780 Thr Asn Ile Leu Gln Tyr Ala Ser Thr Arg Pro Pro Thr Leu Ser 770 775 780

Pro Ile Pro His Ile Pro Arg Ser Pro Tyr Lys Phe Pro Ser Ser 785 790 795 Pro Ile Pro His Ile Pro Arg Ser Pro Tyr Lys Phe Pro Ser Ser 785 790 795

Pro Leu Arg Ile Pro Gly Gly Asn Ile Tyr Ile Ser Pro Leu Lys 800 805 810 Pro Leu Arg Ile Pro Gly Gly Asn Ile Tyr Ile Ser Pro Leu Lys 800 805 810

Ser Pro Tyr Lys Ile Ser Glu Gly Leu Pro Thr Pro Thr Lys Met 815 820 825 Ser Pro Tyr Lys Ile Ser Glu Gly Leu Pro Thr Pro Thr Lys Met 815 820 825

Thr Pro Arg Ser Arg Ile Leu Val Ser Ile Gly Glu Ser Phe Gly 830 835 840 Thr Pro Arg Ser Arg Ile Leu Val Ser Ile Gly Glu Ser Phe Gly 830 835 840

Thr Ser Glu Lys Phe Gln Lys Ile Asn Gln Met Val Cys Asn Ser 845 850 855 Thr Ser Glu Lys Phe Gln Lys Ile Asn Gln Met Val Cys Asn Ser 845 850 855

Asp Arg Val Leu Lys Arg Ser Ala Glu Gly Ser Asn Pro Pro Lys 860 865 870 Asp Arg Val Leu Lys Arg Ser Wing Glu Gly Ser Asn Pro Pro Lys 860 865 870

Pro Leu Lys Lys Leu Arg Phe Asp Ile Glu Gly Ser Asp Glu Ala 875 880 885 Pro Leu Lys Lys Leu Arg Phe Asp Ile Glu Gly Ser Asp Glu Ala 875 880 885

Asp Gly Ser Lys His Leu Pro Gly Glu Ser Lys Phe Gln Gln Lys 890 895 900 Asp Gly Ser Lys His Leu Pro Gly Glu Ser Lys Phe Gln Gln Lys 890 895 900

Leu Ala Glu Met Thr Ser Thr Arg Thr Arg Met Gln Lys Gln Lys 905 910 Leu Ala Glu Met Thr Ser Thr Arg Thr Arg Met Gln Lys Gln Lys 905 910

Met Asn Asp Ser Met Asp Thr Ser Asn Lys Glu Glu Lys 920 925 Met Asn Asp Ser Met Asp Thr Ser Asn Lys Glu Glu Lys 920 925

<210> 71 <210> 71

<211> 1072 <211> 1072

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 71 Met Ala Lys Ala Thr Ser Gly Ala Ala Gly Leu Arg Leu Leu Leu 1 5 10 15 <400> 71 Met Wing Lys Wing Thr Ser Gly Wing Wing Gly Leu Arg Leu Leu Leu 1 5 10 15

Leu Leu Leu Leu Pro Leu Leu Gly Lys Val Ala Leu Gly Leu Tyr 20 25 30 Leu Leu Leu Leu Pro Leu Leu Gly Lys Val Ala Leu Gly Leu Tyr 20 25 30

Phe Ser Arg Asp Ala Tyr Trp Glu Lys Leu Tyr Val Asp Gln Ala 35 40 45 Phe Ser Arg Asp Wing Tyr Trp Glu Lys Leu Tyr Val Asp Gln Wing 35 40 45

Ala Gly Thr Pro Leu Leu Tyr Val His Ala Leu Arg Asp Ala Pro 50 55 60 Wing Gly Thr Pro Leu Leu Tyr Val His Wing Leu Arg Asp Wing Pro 50 55 60

Glu Glu Val Pro Ser Phe Arg Leu Gly Gln His Leu Tyr Gly Thr 65 70 75 Glu Glu Val Pro Ser Phe Arg Leu Gly Gln His Leu Tyr Gly Thr 65 70 75

Tyr Arg Thr Arg Leu His Glu Asn Asn Trp Ile Cys Ile Gln Glu 80 85 90 Tyr Arg Thr Arg Leu His Glu Asn Asn Trp Ile Cys Ile Gln Glu 80 85 90

Asp Thr Gly Leu Leu Tyr Leu Asn Arg Ser Leu Asp His Ser Ser 95 100 105 Asp Thr Gly Leu Leu Tyr Leu Asn Arg Ser Leu Asp His Ser Ser 95 100 105

Trp Glu Lys Leu Ser Val Arg Asn Arg Gly Phe Pro Leu Leu Thr 110 115 120 Trp Glu Lys Leu Ser Val Arg Asn Arg Gly Phe Pro Leu Leu Thr 110 115 120

Val Tyr Leu Lys Val Phe Leu Ser Pro Thr Ser Leu Arg Glu Gly 125 130 135 Val Tyr Leu Lys Val Phe Leu Ser Pro Thr Ser Leu Arg Glu Gly 125 130 135

Glu Cys Gln Trp Pro Gly Cys Ala Arg Val Tyr Phe Ser Phe Phe 140 145 150 Glu Cys Gln Trp Pro Gly Cys Ala Arg Val Tyr Phe Ser Phe Phe 140 145 150

Asn Thr Ser Phe Pro Ala Cys Ser Ser Leu Lys Pro Arg Glu Leu 155 160 165 Asn Thr Ser Phe Pro Ala Cys Ser Ser Leu Lys Pro Arg Glu Leu 155 160 165

Cys Phe Pro Glu Thr Arg Pro Ser Phe Arg Ile Arg Glu Asn Arg 170 175 180 Cys Phe Pro Glu Thr Arg Pro Ser Phe Arg Ile Arg Glu Asn Arg 170 175 180

Pro Pro Gly Thr Phe His Gln Phe Arg Leu Leu Pro Val Gln Phe 185 190 195 Pro Pro Gly Thr Phe His Gln Phe Arg Leu Leu Pro Val Gln Phe 185 190 195

Leu Cys Pro Asn Ile Ser Val Ala Tyr Arg Leu Leu Glu Gly Glu 200 205 210 Leu Cys Pro Asn Ile Ser Val Ala Tyr Arg Leu Leu Glu Gly Glu 200 205 210

Gly Leu Pro Phe Arg Cys Ala Pro Asp Ser Leu Glu Val Ser Thr 215 220 225 Gly Leu Pro Phe Arg Cys Ala Pro Asp Ser Leu Glu Val Ser Thr 215 220 225

Arg Trp Ala Leu Asp Arg Glu Gln Arg Glu Lys Tyr Glu Leu Val 230 235 240 Arg Trp Wing Leu Asp Arg Glu Gln Arg Glu Lys Tyr Glu Leu Val 230 235 240

Ala Val Cys Thr Val His Ala Gly Ala Arg Glu Glu Val Val Met 245 250 255 Wing Val Cys Thr Val His Wing Gly Wing Arg Glu Glu Val Val Met 245 250 255

Val Pro Phe Pro Val Thr Val Tyr Asp Glu Asp Asp Ser Ala Pro 260 265 270 Val Pro Phe Pro Val Thr Val Tyr Asp Glu Asp Asp Ser Ala Pro 260 265 270

Thr Phe Pro Ala Gly Val Asp Thr Ala Ser Ala Val Val Glu Phe 275 280 285 Thr Phe Pro Ala Gly Val Asp Thr Ala Ser Ala Val Val Glu Phe 275 280 285

Lys Arg Lys Glu Asp Thr Val Val Ala Thr Leu Arg Val Phe Asp Lys Arg Lys Glu Asp Thr Val Val Ala Thr Leu Arg Val Phe Asp

290 295 290 295

Ala Asp Val Val Pro Ala Ser Gly Glu Leu Val Arg Arg Tyr Thr 305 310 315 Wing Asp Val Val Pro Wing Ser Gly Glu Leu Val Arg Arg Tyr Thr 305 310 315

Ser Thr Leu Leu Pro Gly Asp Thr Trp Ala Gln Gln Thr Phe Arg 320 325 330 Ser Thr Leu Leu Pro Gly Asp Thr Trp Wing Gln Gln Thr Phe Arg 320 325 330

Val Glu His Trp Pro Asn Glu Thr Ser Val Gln Ala Asn Gly Ser 335 340 345 Val Glu His Trp Pro Asn Glu Thr Ser Val Gln Ala Asn Gly Ser 335 340 345

Phe Val Arg Ala Thr Val His Asp Tyr Arg Leu Val Leu Asn Arg 350 355 360 Phe Val Arg Ala Thr Val His Asp Tyr Arg Leu Val Leu Asn Arg 350 355 360

Asn Leu Ser Ile Ser Glu Asn Arg Thr Met Gln Leu Ala Val Leu 365 370 375 Asn Leu Ser Ile Ser Glu Asn Arg Thr Met Gln Leu Ala Val Leu 365 370 375

Val Asn Asp Ser Asp Phe Gln Gly Pro Gly Ala Gly Val Leu Leu 380 385 390 Val Asn Asp Ser Asp Phe Gln Gly Pro Gly Ala Gly Val Leu Leu 380 385 390

Leu His Phe Asn Val Ser Val Leu Pro Val Ser Leu His Leu Pro 395 400 405 Leu His Phe Asn Val Ser Val Leu Pro Val Ser Leu His Leu Pro 395 400 405

Ser Thr Tyr Ser Leu Ser Val Ser Arg Arg Ala Arg Arg Phe Ala 410 415 420 Ser Thr Tyr Ser Leu Ser Val Ser Arg Arg Ala Arg Arg Phe Ala 410 415 420

Gln Ile Gly Lys Val Cys Val Glu Asn Cys Gln Ala Phe Ser Gly 425 430 435 Gln Ile Gly Lys Val Cys Val Glu Asn Cys Gln Wing Phe Ser Gly 425 430 435

Ile Asn Val Gln Tyr Lys Leu His Ser Ser Gly Ala Asn Cys Ser 440 445 450 Ile Asn Val Gln Tyr Lys Leu His Ser Ser Gly Ala Asn Cys Ser 440 445 450

Thr Leu Gly Val Val Thr Ser Ala Glu Asp Thr Ser Gly Ile Leu 455 460 465 Thr Leu Gly Val Val Thr Ser Ala Glu Asp Thr Ser Gly Ile Leu 455 460 465

Phe Val Asn Asp Thr Lys Ala Leu Arg Arg Pro Lys Cys Ala Glu 470 475 480 Phe Val Asn Asp Thr Lys Ala Leu Arg Arg Pro Lys Cys Ala Glu 470 475 480

Leu His Tyr Met Val Val Ala Thr Asp Gln Gln Thr Ser Arg Gln 485 490 495 Leu His Tyr Met Val Val Wing Thr Asp Gln Gln Thr Ser Arg Gln 485 490 495

Ala Gln Ala Gln Leu Leu Val Thr Val Glu Gly Ser Tyr Val Ala 500 505 510 Gln Wing Gln Wing Leu Leu Val Thr Val Glu Gly Ser Tyr Val Wing 500 505 510

Glu Glu Ala Gly Cys Pro Leu Ser Cys Ala Val Ser Lys Arg Arg 515 520 525 Glu Glu Wing Gly Cys Pro Leu Ser Cys Ala Val Ser Lys Arg Arg 515 520 525

Leu Glu Cys Glu Glu Cys Gly Gly Leu Gly Ser Pro Thr Gly Arg 530 535 540 Leu Glu Cys Glu Glu Cys Gly Gly Leu Gly Ser Pro Thr Gly Arg 530 535 540

Cys Glu Trp Arg Gln Gly Asp Gly Lys Gly Ile Thr Arg Asn Phe 545 550 555 Cys Glu Trp Arg Gln Gly Asp Gly Lys Gly Ile Thr Arg Asn Phe 545 550 555

Ser Thr Cys Ser Pro Ser Thr Lys Thr Cys Pro Asp Gly His Cys 560 565 570 Ser Thr Cys Ser Pro Ser Thr Lys Thr Cys Pro Asp Gly His Cys 560 565 570

Asp Val Val Glu Thr Gln Asp Ile Asn Ile Cys Pro Gln Asp Cys 575 580 585 Asp Val Val Glu Thr Gln Asp Ile Asn Ile Cys Pro Gln Asp Cys 575 580 585

Leu Arg Gly Ser Ile Val Gly Gly His Glu Pro Gly Glu Pro Arg 590 595 600 Leu Arg Gly Ser Ile Val Gly Gly His Glu Pro Gly Glu Pro Arg 590 595 600

Gly Ile Lys Ala Gly Tyr Gly Thr Cys Asn Cys Phe Pro Glu Glu 605 610 615 Gly Ile Lys Wing Gly Tyr Gly Thr Cys Asn Cys Phe Pro Glu Glu 605 610 615

Glu Lys Cys Phe Cys Glu Pro Glu Asp Ile Gln Asp Pro Leu Cys 620 625 Glu Lys Cys Phe Cys Glu Pro Glu Asp Ile Gln Asp Pro Leu Cys 620 625

Asp Glu Leu Cys Arg Thr Val Ile Ala Ala Ala Val Leu Phe Ser 635 640 Asp Glu Leu Cys Arg Thr Val Ile Wing Wing Val Leu Phe Ser 635 640

Phe Ile Val Ser Val Leu Leu Ser Ala Phe Cys Ile His Cys Tyr 650 655 660 Phe Ile Val Ser Val Leu Leu Ser Ala Phe Cys Ile His Cys Tyr 650 655 660

His Lys Phe Ala His Lys Pro Pro Ile Ser Ser Ala Glu Met Thr 665 670 675 His Lys Phe Ala His Lys Pro Pro Ile Ser Ser Ala Glu Met Thr 665 670 675

Phe Arg Arg Pro Ala Gln Ala Phe Pro Val Ser Tyr Ser Ser Ser 680 685 690 Phe Arg Arg Pro Gln Wing Phe Pro Val Ser Tyr Ser Ser Ser 680 685 690

Gly Ala Arg Arg Pro Ser Leu Asp Ser Met Glu Asn Gln Val Ser 695 700 705 Gly Ala Arg Arg Pro Ser Leu Asp Ser Met Glu Asn Gln Val Ser 695 700 705

Val Asp Ala Phe Lys Ile Leu Glu Asp Pro Lys Trp Glu Phe Pro 710 715 720 Val Asp Wing Phe Lys Ile Leu Glu Asp Pro Lys Trp Glu Phe Pro 710 715 720

Arg Lys Asn Leu Val Leu Gly Lys Thr Leu Gly Glu Gly Glu Phe 725 730 735 Arg Lys Asn Leu Val Leu Gly Lys Thr Leu Gly Glu Gly Glu Phe 725 730 735

Gly Lys Val Val Lys Ala Thr Ala Phe His Leu Lys Gly Arg Ala 740 745 750 Gly Lys Val Val Lys Wing Thr Wing Phe His Leu Lys Gly Arg Wing 740 745 750

Gly Tyr Thr Thr Val Ala Val Lys Met Leu Lys Glu Asn Ala Ser 755 760 765 Gly Tyr Thr Thr Val Wing Val Lys Met Leu Lys Glu Asn Wing Ser 755 760 765

Pro Ser Glu Leu Arg Asp Leu Leu Ser Glu Phe Asn Val Leu Lys 770 775 780 Pro Ser Glu Leu Arg Asp Leu Leu Ser Glu Phe Asn Val Leu Lys 770 775 780

Gln Val Asn His Pro His Val Ile Lys Leu Tyr Gly Ala Cys Ser 785 790 795 Gln Val Asn His Pro His Val Ile Lys Leu Tyr Gly Ala Cys Ser 785 790 795

Gln Asp Gly Pro Leu Leu Leu Ile Val Glu Tyr Ala Lys Tyr Gly 800 805 810 Gln Asp Gly Pro Leu Leu Leu Ile Val Glu Tyr Ala Lys Tyr Gly 800 805 810

Ser Leu Arg Gly Phe Leu Arg Glu Ser Arg Lys Val Gly Pro Gly 815 820 825 Ser Leu Arg Gly Phe Leu Arg Glu Ser Arg Lys Val Gly Pro Gly 815 820 825

Tyr Leu Gly Ser Gly Gly Ser Arg Asn Ser Ser Ser Leu Asp His 830 835 840 Tyr Leu Gly Be Gly Gly Be Arg Asn Be Be Be Leu Asp His 830 835 840

Pro Asp Glu Arg Ala Leu Thr Met Gly Asp Leu Ile Ser Phe Ala 845 850 855 Pro Asp Glu Arg Ala Leu Thr Met Gly Asp Leu Ile Ser Phe Ala 845 850 855

Trp Gln Ile Ser Gln Gly Met Gln Tyr Leu Ala Glu Met Lys Leu 860 865 870 Trp Gln Ile Ser Gln Gly Met Gln Tyr Leu Wing Glu Met Lys Leu 860 865 870

Val His Arg Asp Leu Ala Ala Arg Asn Ile Leu Val Ala Glu Gly 875 880 885 Val His Arg Asp Leu Wing Wing Arg Asn Ile Leu Val Wing Glu Gly 875 880 885

Arg Lys Met Lys Ile Ser Asp Phe Gly Leu Ser Arg Asp Val Tyr 890 895 900 Arg Lys Met Lys Ile Ser Asp Phe Gly Leu Ser Arg Asp Val Tyr 890 895 900

Glu Glu Asp Ser Tyr Val Lys Arg Ser Gln Gly Arg Ile Pro Val 905 910 915 Glu Glu Asp Ser Tyr Val Lys Arg Ser Gln Gly Arg Ile Pro Val 905 910 915

Lys Trp Met Ala Ile Glu Ser Leu Phe Asp His Ile Tyr Thr Thr 920 925 930 Lys Trp Met Wing Ile Glu Ser Leu Phe Asp His Ile Tyr Thr Thr 920 925 930

Gln Ser Asp Val Trp Ser Phe Gly Val Leu Leu Trp Glu Ile Val 935 940 945 Gln Ser Asp Val Trp Ser Phe Gly Val Leu Leu Trp Glu Ile Val 935 940 945

Thr Leu Gly Gly Asn Pro Tyr Pro Gly Ile Pro Pro Glu Arg Leu 950 955 960 Thr Leu Gly Gly Asn Pro Tyr Pro Gly Ile Pro Pro Glu Arg Leu 950 955 960

Phe Asn Leu Leu Lys Thr Gly His Arg Met Glu Arg Pro Asp Asn 965 970 Phe Asn Leu Leu Lys Thr Gly His Arg Met Glu Arg Pro Asp Asn 965 970

Cys Ser Glu Glu Met Tyr Arg Leu Met Leu Gln Cys Trp Lys Gln 980 985 Cys Ser Glu Glu Met Tyr Arg Leu Met Leu Gln Cys Trp Lys Gln 980 985

Glu Pro Asp Lys Arg Pro Val Phe Ala Asp Ile Ser Lys Asp Leu 995 1000 1005 Glu Pro Asp Lys Arg Pro Val Phe Ala Asp Ile Ser Lys Asp Leu 995 1000 1005

Glu Lys Met Met Val Lys Arg Arg Asp Tyr Leu Asp Leu Ala Ala 1010 1015 1020 Glu Lys Met Met Val Lys Arg Arg Asp Tyr Leu Asp Leu Wing 1010 1015 1020

Ser Thr Pro Ser Asp Ser Leu Ile Tyr Asp Asp Gly Leu Ser Glu 1025 1030 1035 Ser Thr Pro Ser Asp Ser Leu Ile Tyr Asp Asp Gly Leu Ser Glu 1025 1030 1035

Glu Glu Thr Pro Leu Val Asp Cys Asn Asn Ala Pro Leu Pro Arg 1040 1045 1050 Glu Glu Thr Pro Leu Val Asp Cys Asn Asn Ala Pro Leu Pro Arg 1040 1045 1050

Ala Leu Pro Ser Thr Trp Ile Glu Asn Lys Leu Tyr Gly Arg Ile 1055 1060 1065 Wing Leu Pro Ser Thr Trp Ile Glu Asn Lys Leu Tyr Gly Arg Ile 1055 1060 1065

Ser His Ala Phe Thr Arg Phe 1070 Be His Ala Phe Thr Arg Phe 1070

<210> 72 <210> 72

<211> 403 <211> 403

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 72 Met Asp Arg Ser Lys Glu Asn Cys Ile Ser Gly Pro Val Lys Ala 1 5 10 15 <400> 72 Met Asp Arg Ser Lys Glu Asn Cys Ile Ser Gly Pro Val Lys Wing 1 5 10 15

Thr Ala Pro Val Gly Gly Pro Lys Arg Val Leu Val Thr Gln Gln 20 25 30 Thr Wing Pro Val Gly Gly Pro Lys Arg Val Leu Val Thr Gln Gln 20 25 30

Phe Pro Cys Gln Asn Pro Leu Pro Val Asn Ser Gly Gln Ala Gln 35 40 45 Phe Pro Cys Gln Asn Pro Leu Pro Val Asn Ser Gly Gln Wing Gln 35 40 45

Arg Val Leu Cys Pro Ser Asn Ser Ser Gln Arg Ile Pro Leu Gln 50 55 60 Arg Val Leu Cys Pro Ser Asn Ser Ser Gln Arg Ile Pro Leu Gln 50 55 60

Ala Gln Lys Leu Val Ser Ser His Lys Pro Val Gln Asn Gln Lys 65 70 75 Wing Gln Lys Leu Val Ser Being His Lys Pro Val Gln Asn Gln Lys 65 70 75

Gln Lys Gln Leu Gln Ala Thr Ser Val Pro His Pro Val Ser Arg 80 85 90 Gln Lys Gln Leu Gln Ala Thr Ser Val Pro His Pro Val Ser Arg 80 85 90

Pro Leu Asn Asn Thr Gln Lys Ser Lys Gln Pro Leu Pro Ser Ala 95 100 105 Pro Leu Asn Asn Thr Gln Lys Ser Lys Gln Pro Leu Pro Ser Ala 95 100 105

Pro Glu Asn Asn Pro Glu Glu Glu Leu Ala Ser Lys Gln Lys Asn 110 115 120 Pro Glu Asn Asn Pro Glu Glu Glu Leu Wing Ser Lys Gln Lys Asn 110 115 120

Glu Glu Ser Lys Lys Arg Gln Trp Ala Leu Glu Asp Phe Glu Ile 125 130 135 Glu Glu Ser Lys Lys Arg Gln Trp Wing Leu Glu Asp Phe Glu Ile 125 130 135

Gly Arg Pro Leu Gly Lys Gly Lys Phe Gly Asn Val Tyr Leu Ala 140 145 150 Gly Arg Pro Leu Gly Lys Gly Lys Phe Gly Asn Val Tyr Leu Wing 140 145 150

Arg Glu Lys Gln Ser Lys Phe Ile Leu Ala Leu Lys Val Leu Phe 155 160 165 Arg Glu Lys Gln Ser Lys Phe Ile Leu Ala Leu Lys Val Leu Phe 155 160 165

Lys Ala Gln Leu Glu Lys Ala Gly Val Glu His Gln Leu Arg Arg 170 175 180 Lys Wing Gln Leu Glu Lys Wing Gly Val Glu His Gln Leu Arg Arg 170 175 180

Glu Val Glu Ile Gln Ser His Leu Arg His Pro Asn Ile Leu Arg 185 190 195 Glu Val Glu Ile Gln Ser His Leu Arg His Pro Asn Ile Leu Arg 185 190 195

Leu Tyr Gly Tyr Phe His Asp Ala Thr Arg Val Tyr Leu Ile Leu 200 205 210 Leu Tyr Gly Tyr Phe His Asp Ala Thr Arg Val Tyr Leu Ile Leu 200 205 210

Glu Tyr Ala Pro Leu Gly Thr Val Tyr Arg Glu Leu Gln Lys Leu 215 220 225 Glu Tyr Ala Pro Leu Gly Thr Val Tyr Arg Glu Leu Gln Lys Leu 215 220 225

Ser Lys Phe Asp Glu Gln Arg Thr Ala Thr Tyr Ile Thr Glu Leu 230 235 240 Ser Lys Phe Asp Glu Gln Arg Thr Ala Thr Tyr Ile Thr Glu Leu 230 235 240

Ala Asn Ala Leu Ser Tyr Cys His Ser Lys Arg Val Ile His Arg 245 250 255 Ala Asn Ala Leu Ser Tyr Cys His Ser Lys Arg Val Ile His Arg 245 250 255

Asp Ile Lys Pro Glu Asn Leu Leu Leu Gly Ser Ala Gly Glu Leu 260 265 270 Asp Ile Lys Pro Glu Asn Leu Leu Leu Gly Ser Ala Gly Glu Leu 260 265 270

Lys Ile Ala Asp Phe Gly Trp Ser Val His Ala Pro Ser Ser Arg 275 280 285 Lys Ile Ala Asp Phe Gly Trp Ser Val His Ala Pro Ser Ser Arg 275 280 285

Arg Thr Thr Leu Cys Gly Thr Leu Asp Tyr Leu Pro Pro Glu Met 290 295 300 Arg Thr Thr Leu Cys Gly Thr Leu Asp Tyr Leu Pro Pro Glu Met 290 295 300

Ile Glu Gly Arg Met His Asp Glu Lys Val Asp Leu Trp Ser Leu 305 310 315 Ile Glu Gly Arg Met His Asp Glu Lys Val Asp Leu Trp Ser Leu 305 310 315

Gly Val Leu Cys Tyr Glu Phe Leu Val Gly Lys Pro Pro Phe Glu 320 325 330 Gly Val Leu Cys Tyr Glu Phe Leu Val Gly Lys Pro Pro Phe Glu 320 325 330

Ala Asn Thr Tyr Gln Glu Thr Tyr Lys Arg Ile Ser Arg Val Glu 335 340 345 Wing Asn Thr Tyr Gln Glu Thr Tyr Lys Arg Ile Ser Arg Val Glu 335 340 345

Phe Thr Phe Pro Asp Phe Val Thr Glu Gly Ala Arg Asp Leu Ile 350 355 360 Phe Thr Phe Pro Asp Phe Val Thr Glu Gly Ala Arg Asp Leu Ile 350 355 360

Ser Arg Leu Leu Lys His Asn Pro Ser Gln Arg Pro Met Leu Arg 365 370 375 Ser Arg Leu Leu Lys His Asn Pro Ser Gln Arg Pro Met Leu Arg 365 370 375

Glu Val Leu Glu His Pro Trp Ile Thr Ala Asn Ser Ser Lys Pro 380 385 390 Glu Val Leu Glu His Pro Trp Ile Thr Ala Asn Ser Ser Lys Pro 380 385 390

Ser Asn Cys Gln Asn Lys Glu Ser Ala Ser Lys Gln Ser 395 400 Be Asn Cys Gln Asn Lys Glu Be Ala Be Lys Gln Ser 395 400

<210> 73 <210> 73

<211> 567 <211> 567

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 73 Met Gly Arg Gly Leu Leu Arg Gly Leu Trp Pro Leu His Ile Val 1 5 10 15 <400> 73 Met Gly Arg Gly Leu Leu Arg Gly Leu Trp Pro Leu His Ile Val 1 5 10 15

Leu Trp Thr Arg Ile Ala Ser Thr Ile Pro Pro His Val Gln Lys 20 25 30 Leu Trp Thr Arg Ile Ala Ser Thr Ile Pro Pro His Val Gln Lys 20 25 30

Ser Val Asn Asn Asp Met Ile Val Thr Asp Asn Asn Gly Ala Val 35 40 45 Ser Val Asn Asn Asp Met Ile Val Thr Asp Asn Asn Gly Ala Val 35 40 45

Lys Phe Pro Gln Leu Cys Lys Phe Cys Asp Val Arg Phe Ser Thr 50 55 60 Lys Phe Pro Gln Leu Cys Lys Phe Cys Asp Val Arg Phe Ser Thr 50 55 60

Cys Asp Asn Gln Lys Ser Cys Met Ser Asn Cys Ser Ile Thr Ser 65 70 75 Cys Asp Asn Gln Lys Ser Cys Met Ser Asn Cys Ser Ile Thr Ser 65 70 75

Ile Cys Glu Lys Pro Gln Glu Val Cys Val Ala Val Trp Arg Lys 80 85 90 Ile Cys Glu Lys Pro Gln Glu Val Cys Val Ala Val Trp Arg Lys 80 85 90

Asn Asp Glu Asn Ile Thr Leu Glu Thr Val Cys His Asp Pro Lys 95 100 105 Leu Pro Tyr His Asp Phe Ile Leu Glu Asp Ala Ala Ser Pro Lys 110 115 Asn Asp Glu Asn Ile Thr Leu Glu Thr Val Cys His Asp Pro Lys 95 100 105 Leu Pro Tyr His Asp Phe Ile Leu Glu Asp Wing Be Pro Lys 110 115

Cys Ile Met Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe Met 125 130 135 Cys Ile Met Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe Met 125 130 135

Cys Ser Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser 140 145 150 Cys Ser Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser 140 145 150

Glu Glu Tyr Asn Thr Ser Asn Pro Asp Leu Leu Leu Val Ile Phe 155 160 165 Glu Glu Tyr Asn Thr Ser Asn Pro Asp Leu Leu Leu Val Ile Phe 155 160 165

Gln Val Thr Gly Ile Ser Leu Leu Pro Pro Leu Gly Val Ala Ile 170 175 180 Gln Val Thr Gly Ile Ser Leu Leu Pro Pro Leu Gly Val Wing Ile 170 175 180

Ser Val Ile Ile Ile Phe Tyr Cys Tyr Arg Val Asn Arg Gln Gln 185 190 195 Ser Val Ile Ile Ile Phe Tyr Cys Tyr Arg Val Asn Arg Gln Gln 185 190 195

Lys Leu Ser Ser Thr Trp Glu Thr Gly Lys Thr Arg Lys Leu Met 200 205 210 Lys Leu Ser Ser Thr Trp Glu Thr Gly Lys Thr Arg Lys Leu Met 200 205 210

Glu Phe Ser Glu His Cys Ala Ile Ile Leu Glu Asp Asp Arg Ser 215 220 225 Glu Phe Ser Glu His Cys Ile Wing Ile Leu Glu Asp Asp Arg Ser 215 220 225

Asp Ile Ser Ser Thr Cys Ala Asn Asn Ile Asn His Asn Thr Glu 230 235 240 Asp Ile Ser Ser Thr Cys Ala Asn Asn Ile Asn His Asn Thr Glu 230 235 240

Leu Leu Pro Ile Glu Leu Asp Thr Leu Val Gly Lys Gly Arg Phe 245 250 255 Leu Leu Pro Ile Glu Leu Asp Thr Leu Val Gly Lys Gly Arg Phe 245 250 255

Ala Glu Val Tyr Lys Ala Lys Leu Lys Gln Asn Thr Ser Glu Gln 260 265 270 Wing Glu Val Tyr Lys Wing Lys Leu Lys Gln Asn Thr Ser Glu Gln 260 265 270

Phe Glu Thr Val Ala Val Lys Ile Phe Pro Tyr Glu Glu Tyr Ala 275 280 285 Phe Glu Thr Val Ala Val Lys Ile Phe Pro Tyr Glu Glu Tyr Ala 275 280 285

Ser Trp Lys Thr Glu Lys Asp Ile Phe Ser Asp Ile Asn Leu Lys 290 295 300 Be Trp Lys Thr Glu Lys Asp Ile Phe Be Asp Ile Asn Leu Lys 290 295 300

His Glu Asn Ile Leu Gln Phe Leu Thr Ala Glu Glu Arg Lys Thr 305 310 315 His Glu Asn Ile Leu Gln Phe Leu Thr Wing Glu Glu Arg Lys Thr 305 310 315

Glu Leu Gly Lys Gln Tyr Trp Leu Ile Thr Ala Phe His Ala Lys 320 325 330 Glu Leu Gly Lys Gln Tyr Trp Leu Ile Thr Ala Phe His Ala Lys 320 325 330

Gly Asn Leu Gln Glu Tyr Leu Thr Arg His Val Ile Ser Trp Glu 335 340 345 Gly Asn Leu Gln Glu Tyr Leu Thr Arg His Val Ile Ser Trp Glu 335 340 345

Asp Leu Arg Lys Leu Gly Ser Ser Leu Ala Arg Gly Ile Ala His 350 355 360 Asp Leu Arg Lys Leu Gly Ser Ser Leu Ala Arg Gly Ile His His 350 355 360

Leu His Ser Asp His Thr Pro Cys Gly Arg Pro Lys Met Pro Ile 365 370 375 Leu His Ser Asp His Thr Pro Cys Gly Arg Pro Lys Met Pro Ile 365 370 375

Val His Arg Asp Leu Lys Ser Ser Asn Ile Leu Val Lys Asn Asp 380 385 390 Val His Arg Asp Leu Lys Being Ser Asn Ile Leu Val Lys Asn Asp 380 385 390

Leu Thr Cys Cys Leu Cys Asp Phe Gly Leu Ser Leu Arg Leu Asp 395 400 405 Leu Thr Cys Cys Leu Cys Asp Phe Gly Leu Ser Leu Arg Leu Asp 395 400 405

Pro Thr Leu Ser Val Asp Asp Leu Ala Asn Ser Gly Gln Val Gly 410 415 420 Pro Thr Leu Ser Val Asp Asp Leu Ala Asn Ser Gly Gln Val Gly 410 415 420

Thr Ala Arg Tyr Met Ala Pro Glu Val Leu Glu Ser Arg Met Asn 425 430 435 Thr Wing Arg Tyr Met Wing Pro Glu Val Leu Glu Ser Arg Met Asn 425 430 435

Leu Glu Asn Ala Glu Ser Phe Lys Gln Thr Asp Val Tyr Ser Met 440 445 Leu Glu Asn Wing Glu Ser Phe Lys Gln Thr Asp Val Tyr Ser Met 440 445

Ala Leu Val Leu Trp Glu Met Thr Ser Arg Cys Asn Ala Val Gly 455 460 465 Wing Leu Val Leu Trp Glu Met Thr Ser Arg Cys Asn Wing Val Gly 455 460 465

Glu Val Lys Asp Tyr Glu Pro Pro Phe Gly Ser Lys Val Arg Glu 470 475 480 Glu Val Lys Asp Tyr Glu Pro Pro Phe Gly Ser Lys Val Arg Glu 470 475 480

His Pro Cys Val Glu Ser Met Lys Asp Asn Val Leu Arg Asp Arg 485 490 495 His Pro Cys Val Glu Ser Met Lys Asp Asn Val Leu Arg Asp Arg 485 490 495

Gly Arg Pro Glu Ile Pro Ser Phe Trp Leu Asn His Gln Gly Ile 500 505 510 Gly Arg Pro Glu Ile Pro Ser Phe Trp Leu Asn His Gln Gly Ile 500 505 510

Gln Met Val Cys Glu Thr Leu Thr Glu Cys Trp Asp His Asp Pro 515 520 525 Gln Met Val Cys Glu Thr Leu Thr Glu Cys Trp Asp His Asp Pro 515 520 525

Glu Ala Arg Leu Thr Ala Gln Cys Val Ala Glu Arg Phe Ser Glu 530 535 540 Glu Wing Arg Leu Thr Wing Gln Cys Val Wing Glu Arg Phe Ser Glu 530 535 540

Leu Glu His Leu Asp Arg Leu Ser Gly Arg Ser Cys Ser Glu Glu 545 550 555 Leu Glu His Leu Asp Arg Leu Ser Gly Arg Ser Cys Ser Glu Glu 545 550 555

Lys Ile Pro Glu Asp Gly Ser Leu Asn Thr Thr Lys 560 565 Lys Ile Pro Glu Asp Gly Ser Leu Asn Thr Thr Lys 560 565

<210> 74 <210> 74

<211> 393 <211> 393

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 74 Met Glu Glu Pro Gln Ser Asp Pro Ser Val Glu Pro Pro Leu Ser 1 5 10 15 <400> 74 Met Glu Glu Pro Gln Ser Asp Pro Ser Val Glu Pro Pro Leu Ser 1 5 10 15

Asp Glu Ala Pro Arg Met Pro Glu Ala Ala Pro Arg Val Ala Pro 65 70 75 Asp Glu Ala Pro Arg Met Pro Glu Ala Pro Wing Arg Val Ala Pro 65 70 75

Asp Ser Asp Asp Be Asp

<210> 75 <210> 75

<211> 1308 <211> 1308

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 75 Met Lys Pro Ala Thr Gly Leu Trp Val Trp Val Ser Leu Leu Val 1 5 10 15 <400> 75 Met Lys Pro Wing Thr Gly Leu Trp Val Trp Val Ser Leu Leu Val 1 5 10 15

Phe Leu Arg Ser Val Arg Glu Val Thr Gly Tyr Val Leu Val Ala 80 85 90 Leu Asn Gln Phe Arg Tyr Leu Pro Leu Glu Asn Leu Arg Ile Ile 95 100 Phe Leu Arg Ser Val Arg Glu Val Thr Gly Tyr Val Leu Val Wing 80 85 90 Leu Asn Gln Phe Arg Tyr Leu Pro Leu Glu Asn Leu Arg Ile Ile 95 100

Thr Thr Phe Gln Leu Glu His Asn Phe Asn Ala Lys Tyr Thr Tyr 275 280 285 Thr Thr Phe Gln Leu Glu His Asn Phe Asn Ala Lys Tyr Thr Tyr 275 280 285

Val Thr Ile Gly Gly Arg Val Leu Tyr Ser Gly Leu Ser Leu Leu 425 430 Val Thr Ile Gly Gly Arg Val Leu Tyr Ser Gly Leu Ser Leu Leu 425 430

Ile Leu Lys Gln Gln Gly Ile Thr Ser Leu Gln Phe Gln Ser Leu 440 445 Ile Leu Lys Gln Gln Gly Ile Thr Ser Leu Gln Phe Gln Ser Leu 440 445

Asn Ser Phe Ile Phe Lys Tyr Ala Asp Pro Asp Arg Glu Cys His 605 610 615 Asn Ser Phe Ile Phe Lys Tyr Ala Asp Pro Asp Arg Glu Cys His 605 610 615

Pro Cys His Pro Asn Cys Thr Gln Gly Cys Asn Gly Pro Thr Ser 620 625 630 Pro Cys His Pro Asn Cys Thr Gln Gly Cys Asn Gly Pro Thr Ser 620 625 630

Met Asp Glu Ala Leu Ile Met Ala Ser Met Asp His Pro His Leu Met Asp Glu Ala Leu Ile Met Ala Ser Met Asp His Pro His Leu

770 775 770 775

Thr Ile Asp Val Tyr Met Val Met Val Lys Cys Trp Met Ile Asp 950 955 960 Thr Ile Asp Val Tyr Met Val Met Val Lys Cys Trp Met Ile Asp 950 955 960

Ala Asp Ser Arg Pro Lys Phe Lys Glu Leu Ala Ala Glu Phe Ser 965 970 975 Wing Asp Ser Arg Pro Lys Phe Lys Glu Leu Wing Glu Phe Ser 965 970 975

Arg Met Ala Arg Asp Pro Gln Arg Tyr Leu Val Ile Gln Gly Asp 980 985 990 Arg Met Wing Arg Asp Pro Gln Arg Tyr Leu Val Ile Gln Gly Asp 980 985 990

Lys Pro Gly Thr Val Leu Pro Pro Pro Pro Tyr Arg His Arg Asn 1295 1300 1305 Lys Pro Gly Thr Val Leu Pro Pro Pro Pro Tyr Arg His Arg Asn 1295 1300 1305

Thr Val Val Thr Val Val

<210> 76 <210> 76

<211> 821 <211> 821

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 76 Met Val Ser Trp Gly Arg Phe Ile Cys Leu Val Val Val Thr Met 1 5 10 15 <400> 76 Met Val Ser Trp Gly Arg Phe Ile Cys Leu Val Val Val Thr Met 1 5 10 15

Ala Thr Leu Ser Leu Ala Arg Pro Ser Phe Ser Leu Val Glu Asp 20 25 30 Ala Thr Leu Ser Leu Ala Arg Pro Ser Phe Ser Leu Val Glu Asp 20 25 30

Thr Thr Leu Glu Pro Glu Glu Pro Pro Thr Lys Tyr Gln Ile Ser 35 40 45 Thr Thr Leu Glu Pro Glu Glu Pro Pro Thr Lys Tyr Gln Ile Ser 35 40 45

Gln Pro Glu Val Tyr Val Ala Ala Pro Gly Glu Ser Leu Glu Val 50 55 60 Gln Pro Glu Val Tyr Val Ala Wing Pro Gly Glu Ser Leu Glu Val 50 55 60

Arg Cys Leu Leu Lys Asp Ala Ala Val Ile Ser Trp Thr Lys Asp 65 70 75 Arg Cys Leu Leu Lys Asp Wing Wing Val Ile Ser Trp Thr Lys Asp 65 70 75

Gly Val His Leu Gly Pro Asn Asn Arg Thr Val Leu Ile Gly Glu 80 85 90 Gly Val His Leu Gly Pro Asn Asn Arg Thr Val Leu Ile Gly Glu 80 85 90

Tyr Leu Gln Ile Lys Gly Ala Thr Pro Arg Asp Ser Gly Leu Tyr 95 100 105 Ala Cys Thr Ala Ser Arg Thr Val Asp Ser Glu Thr Trp Tyr Phe 110 115 Tyr Leu Gln Ile Lys Gly Ala Thr Pro Arg Asp Ser Gly Leu Tyr 95 100 105 Ala Cys Thr Ala Ser Arg Thr Val Asp Ser Glu Thr Trp Tyr Phe 110 115

Met Val Asn Val Thr Asp Ala Ile Ser Ser Gly Asp Asp Glu Asp 125 130 135 Met Val Asn Val Thr Asp Wing Ile Ser Be Gly Asp Asp Glu Asp 125 130 135

Asp Thr Asp Gly Ala Glu Asp Phe Val Ser Glu Asn Ser Asn Asn 140 145 150 Asp Thr Asp Gly Ala Glu Asp Phe Val Ser Glu Asn Ser Asn Asn 140 145 150

Lys Arg Ala Pro Tyr Trp Thr Asn Thr Glu Lys Met Glu Lys Arg 155 160 165 Lys Arg Ala Pro Tyr Trp Thr Asn Thr Glu Lys Met Glu Lys Arg 155 160 165

Leu His Ala Val Pro Ala Ala Asn Thr Val Lys Phe Arg Cys Pro 170 175 180 Leu His Wing Val Pro Wing Wing Asn Thr Val Lys Phe Arg Cys Pro 170 175 180

Ala Gly Gly Asn Pro Met Pro Thr Met Arg Trp Leu Lys Asn Gly 185 190 195 Wing Gly Gly Asn Pro Met Pro Thr Met Arg Trp Leu Lys Asn Gly 185 190 195

Lys Glu Phe Lys Gln Glu His Arg Ile Gly Gly Tyr Lys Val Arg 200 205 210 Lys Glu Phe Lys Gln Glu His Arg Ile Gly Gly Tyr Lys Val Arg 200 205 210

Asn Gln His Trp Ser Leu Ile Met Glu Ser Val Val Pro Ser Asp 215 220 225 Asn Gln His Trp Ser Leu Ile Met Glu Ser Val Val Pro Ser Asp 215 220 225

Lys Gly Asn Tyr Thr Cys Val Val Glu Asn Glu Tyr Gly Ser Ile 230 235 240 Lys Gly Asn Tyr Thr Cys Val Val Glu Asn Glu Tyr Gly Ser Ile 230 235 240

Asn His Thr Tyr His Leu Asp Val Val Glu Arg Ser Pro His Arg 245 250 255 Asn His Thr Tyr His Leu Asp Val Val Glu Arg Ser Pro His Arg 245 250 255

Pro Ile Leu Gln Ala Gly Leu Pro Ala Asn Ala Ser Thr Val Val 260 265 270 Pro Ile Leu Gln Wing Gly Leu Pro Wing Asn Wing Ser Thr Val Val 260 265 270

Gly Gly Asp Val Glu Phe Val Cys Lys Val Tyr Ser Asp Ala Gln 275 280 285 Gly Gly Asp Val Glu Phe Val Cys Lys Val Tyr Ser Asp Wing Gln 275 280 285

Pro His Ile Gln Trp Ile Lys His Val Glu Lys Asn Gly Ser Lys 290 295 300 Pro His Ile Gln Trp Ile Lys His Val Glu Lys Asn Gly Ser Lys 290 295 300

Tyr Gly Pro Asp Gly Leu Pro Tyr Leu Lys Val Leu Lys Ala Ala 305 310 315 Tyr Gly Pro Asp Gly Leu Pro Tyr Leu Lys Val Leu Lys Wing Wing 305 310 315

Gly Val Asn Thr Thr Asp Lys Glu Ile Glu Val Leu Tyr Ile Arg 320 325 330 Gly Val Asn Thr Thr Asp Lys Glu Ile Glu Val Leu Tyr Ile Arg 320 325 330

Asn Val Thr Phe Glu Asp Ala Gly Glu Tyr Thr Cys Leu Ala Gly 335 340 345 Asn Val Thr Phe Glu Asp Wing Gly Glu Tyr Thr Cys Leu Wing Gly 335 340 345

Asn Ser Ile Gly Ile Ser Phe His Ser Ala Trp Leu Thr Val Leu 350 355 360 Asn Ser Ile Gly Ile Ser Phe His Ser Ala Trp Leu Thr Val Leu 350 355 360

Pro Ala Pro Gly Arg Glu Lys Glu Ile Thr Ala Ser Pro Asp Tyr 365 370 375 Pro Wing Pro Gly Arg Glu Lys Glu Ile Thr Ala Ser Pro Asp Tyr 365 370 375

Leu Glu Ile Ala Ile Tyr Cys Ile Gly Val Phe Leu Ile Ala Cys 380 385 390 Leu Glu Ile Wing Ile Tyr Cys Ile Gly Val Phe Leu Ile Wing Cys 380 385 390

Met Val Val Thr Val Ile Leu Cys Arg Met Lys Asn Thr Thr Lys 395 400 405 Met Val Val Thr Val Ile Leu Cys Arg Met Lys Asn Thr Thr Lys 395 400 405

Lys Pro Asp Phe Ser Ser Gln Pro Ala Val His Lys Leu Thr Lys 410 415 420 Lys Pro Asp Phe Ser Ser Gln Pro Ala Val His Lys Leu Thr Lys 410 415 420

Arg Ile Pro Leu Arg Arg Gln Val Thr Val Ser Ala Glu Ser Ser 425 430 435 Arg Ile Pro Leu Arg Arg Gln Val Thr Val Ser Ala Glu Ser Ser 425 430 435

Ser Ser Met Asn Ser Asn Thr Pro Leu Val Arg Ile Thr Thr Arg Be Be Met Asn Be Asn Thr Pro Leu Val Arg Ile Thr Thr Arg

440 445 440 445

Leu Ser Ser Thr Ala Asp Thr Pro Met Leu Ala Gly Val Ser Glu 455 460 465 Leu Ser Ser Thr Wing Asp Thr Pro Met Leu Wing Gly Val Ser Glu 455 460 465

Tyr Glu Leu Pro Glu Asp Pro Lys Trp Glu Phe Pro Arg Asp Lys 470 475 480 Tyr Glu Leu Pro Glu Asp Pro Lys Trp Glu Phe Pro Arg Asp Lys 470 475 480

Leu Thr Leu Gly Lys Pro Leu Gly Glu Gly Cys Phe Gly Gln Val 485 490 495 Leu Thr Leu Gly Lys Pro Leu Gly Glu Gly Cys Phe Gly Gln Val 485 490 495

Val Met Ala Glu Ala Val Gly Ile Asp Lys Asp Lys Pro Lys Glu 500 505 510 Val Met Wing Glu Wing Val Gly Ile Asp Lys Asp Lys Pro Lys Glu 500 505 510

Ala Val Thr Val Ala Val Lys Met Leu Lys Asp Asp Ala Thr Glu 515 520 525 Wing Val Thr Val Wing Val Lys Met Leu Lys Asp Asp Wing Thr Glu 515 520 525

Lys Asp Leu Ser Asp Leu Val Ser Glu Met Glu Met Met Lys Met 530 535 540 Lys Asp Leu Ser Asp Leu Val Ser Glu Met Glu Met Met Lys Met 530 535 540

Ile Gly Lys His Lys Asn Ile Ile Asn Leu Leu Gly Ala Cys Thr 545 550 555 Ile Gly Lys His Lys Asn Ile Ile Asn Leu Leu Gly Ala Cys Thr 545 550 555

Gln Asp Gly Pro Leu Tyr Val Ile Val Glu Tyr Ala Ser Lys Gly 560 565 570 Gln Asp Gly Pro Leu Tyr Val Ile Val Glu Tyr Ala Ser Lys Gly 560 565 570

Asn Leu Arg Glu Tyr Leu Arg Ala Arg Arg Pro Pro Gly Met Glu 575 580 585 Asn Leu Arg Glu Tyr Leu Arg Ala Arg Arg Pro Pro Gly Met Glu 575 580 585

Tyr Ser Tyr Asp Ile Asn Arg Val Pro Glu Glu Gln Met Thr Phe 590 595 600 Tyr Ser Tyr Asp Ile Asn Arg Val Pro Glu Glu Gln Met Thr Phe 590 595 600

Lys Asp Leu Val Ser Cys Thr Tyr Gln Leu Ala Arg Gly Met Glu 605 610 615 Lys Asp Leu Val Ser Cys Thr Tyr Gln Leu Ala Arg Gly Met Glu 605 610 615

Tyr Leu Ala Ser Gln Lys Cys Ile His Arg Asp Leu Ala Ala Arg 620 625 630 Tyr Leu Ala Ser Gln Lys Cys Ile His Arg Asp Leu Ala Ala Arg 620 625 630

Asn Val Leu Val Thr Glu Asn Asn Val Met Lys Ile Ala Asp Phe 635 640 645 Asn Val Leu Val Thr Glu Asn Asn Val Met Lys Ile Wing Asp Phe 635 640 645

Gly Leu Ala Arg Asp Ile Asn Asn Ile Asp Tyr Tyr Lys Lys Thr 650 655 660 Gly Leu Ala Arg Asp Ile Asn Asn Ile Asp Tyr Tyr Lys Lys Thr 650 655 660

Thr Asn Gly Arg Leu Pro Val Lys Trp Met Ala Pro Glu Ala Leu 665 670 675 Thr Asn Gly Arg Leu Pro Val Lys Trp Met Ala Pro Glu Ala Leu 665 670 675

Phe Asp Arg Val Tyr Thr His Gln Ser Asp Val Trp Ser Phe Gly 680 685 690 Phe Asp Arg Val Tyr Thr His Gln Ser Asp Val Trp Ser Phe Gly 680 685 690

Val Leu Met Trp Glu Ile Phe Thr Leu Gly Gly Ser Pro Tyr Pro 695 700 705 Val Leu Met Trp Glu Ile Phe Thr Leu Gly Gly Ser Pro Tyr Pro 695 700 705

Gly Ile Pro Val Glu Glu Leu Phe Lys Leu Leu Lys Glu Gly His 710 715 720 Gly Ile Pro Val Glu Glu Leu Phe Lys Leu Leu Lys Glu Gly His 710 715 720

Arg Met Asp Lys Pro Ala Asn Cys Thr Asn Glu Leu Tyr Met Met 725 730 735 Arg Met Asp Lys Pro Wing Asn Cys Thr Asn Glu Leu Tyr Met Met 725 730 735

Met Arg Asp Cys Trp His Ala Val Pro Ser Gln Arg Pro Thr Phe 740 745 750 Met Arg Asp Cys Trp His Ala Val Pro Ser Gln Arg Pro Thr Phe 740 745 750

Lys Gln Leu Val Glu Asp Leu Asp Arg Ile Leu Thr Leu Thr Thr 755 760 765 Lys Gln Leu Val Glu Asp Leu Asp Arg Ile Leu Thr Leu Thr Thr 755 760 765

Asn Glu Glu Tyr Leu Asp Leu Ser Gln Pro Leu Glu Gln Tyr Ser 770 775 Asn Glu Glu Tyr Leu Asp Leu Ser Gln Pro Leu Glu Gln Tyr Ser 770 775

Pro Ser Tyr Pro Asp Thr Arg Ser Ser Cys Ser Ser Gly Asp Asp 785 790 795 Pro Be Tyr Pro Asp Thr Arg Be Be Cys Be Be Gly Asp Asp 785 790 795

Ser Val Phe Ser Pro Asp Pro Met Pro Tyr Glu Pro Cys Leu Pro 800 805 810 Ser Val Phe Ser Pro Asp Pro Met Pro Tyr Glu Pro Cys Leu Pro 800 805 810

Gln Tyr Pro His Ile Asn Gly Ser Val Lys Thr 815 820 Gln Tyr Pro His Ile Asn Gly Ser Val Lys Thr 815 820

<210> 77 <210> 77

<211> 1166 <211> 1166

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 77 Met Ala Asn Asp Ser Pro Ala Lys Ser Leu Val Asp Ile Asp Leu 1 5 10 15 <400> 77 Met Wing Asn Asp Ser Pro Wing Lys Ser Leu Val Asp Ile Asp Leu 1 5 10 15

Ser Ser Leu Arg Asp Pro Ala Gly Ile Phe Glu Leu Val Glu Val 20 25 30 Be Ser Leu Arg Asp Pro Wing Gly Ile Phe Glu Leu Val Glu Val 20 25 30

Val Gly Asn Gly Thr Tyr Gly Gln Val Tyr Lys Gly Arg His Val 35 40 45 Val Gly Asn Gly Thr Tyr Gly Gln Val Tyr Lys Gly Arg His Val 35 40 45

Lys Thr Gly Gln Leu Ala Ala Ile Lys Val Met Asp Val Thr Glu 50 55 60 Lys Thr Gly Gln Leu Wing Ile Lys Val Met Asp Val Thr Glu 50 55 60

Asp Glu Glu Glu Glu Ile Lys Leu Glu Ile Asn Met Leu Lys Lys 65 70 75 Asp Glu Glu Glu Glu Ile Lys Leu Glu Ile Asn Met Leu Lys Lys 65 70 75

Tyr Ser His His Arg Asn Ile Ala Thr Tyr Tyr Gly Ala Phe Ile 80 85 90 Tyr Ser His His Arg Asn Ile Ala Thr Tyr Tyr Gly Ala Phe Ile 80 85 90

Lys Lys Ser Pro Pro Gly His Asp Asp Gln Leu Trp Leu Val Met 95 100 105 Lys Lys Ser Pro Pro Gly His Asp Asp Gln Leu Trp Leu Val Met 95 100 105

Glu Phe Cys Gly Ala Gly Ser Ile Thr Asp Leu Val Lys Asn Thr 110 115 120 Glu Phe Cys Gly Ala Gly Ser Ile Thr Asp Leu Val Lys Asn Thr 110 115 120

Lys Gly Asn Thr Leu Lys Glu Asp Trp Ile Ala Tyr Ile Ser Arg 125 130 135 Lys Gly Asn Thr Leu Lys Glu Asp Trp Ile Wing Tyr Ile Ser Arg 125 130 135

Glu Ile Leu Arg Gly Leu Ala His Leu His Ile His His Val Ile 140 145 150 Glu Ile Leu Arg Gly Leu Wing His Leu His Ile His His Val Ile 140 145 150

His Arg Asp Ile Lys Gly Gln Asn Val Leu Leu Thr Glu Asn Ala 155 160 165 His Arg Asp Ile Lys Gly Gln Asn Val Leu Leu Thr Glu Asn Wing 155 160 165

Glu Val Lys Leu Val Asp Phe Gly Val Ser Ala Gln Leu Asp Arg 170 175 180 Glu Val Lys Leu Val Asp Phe Gly Val Ser Wing Gln Leu Asp Arg 170 175 180

Thr Val Gly Arg Arg Asn Thr Phe Ile Gly Thr Pro Tyr Trp Met 185 190 195 Thr Val Gly Arg Arg Asn Thr Phe Ile Gly Thr Pro Tyr Trp Met 185 190 195

Ala Pro Glu Val Ile Ala Cys Asp Glu Asn Pro Asp Ala Thr Tyr 200 205 210 Ala Pro Glu Val Ile Ala Cys Asp Glu Asn Pro Asp Ala Thr Tyr 200 205 210

Asp Tyr Arg Ser Asp Leu Trp Ser Cys Gly Ile Thr Ala Ile Glu 215 220 225 Asp Tyr Arg Ser Asp Leu Trp Ser Cys Gly Ile Thr Ile Glu Glu 220 220 225

Met Ala Glu Gly Ala Pro Pro Leu Cys Asp Met His Pro Met Arg 230 235 240 Met Wing Glu Gly Wing Pro Pro Leu Cys Asp Met His Pro Met Arg 230 235 240

Ala Leu Phe Leu Ile Pro Arg Asn Pro Pro Pro Arg Leu Lys Ser 245 250 255 Wing Leu Phe Leu Ile Pro Arg Asn Pro Pro Pro Arg Leu Lys Ser 245 250 255

Lys Lys Trp Ser Lys Lys Phe Phe Ser Phe Ile Glu Gly Cys Leu 260 265 270 Val Lys Asn Tyr Met Gln Arg Pro Ser Thr Glu Gln Leu Leu Lys 275 280 Lys Lys Trp Ser Lys Lys Phe Phe Ser Phe Ile Glu Gly Cys Leu 260 265 270 Val Lys Asn Tyr Met Gln Arg Pro Ser Thr Glu Gln Leu Leu Lys 275 280

His Pro Phe Ile Arg Asp Gln Pro Asn Glu Arg Gln Val Arg Ile 290 295 300 His Pro Phe Ile Arg Asp Gln Pro Asn Glu Arg Gln Val Arg Ile 290 295 300

Gln Leu Lys Asp His Ile Asp Arg Thr Arg Lys Lys Arg Gly Glu 305 310 315 Gln Leu Lys Asp His Ile Asp Arg Thr Arg Lys Lys Arg Gly Glu 305 310 315

Lys Asp Glu Thr Glu Tyr Glu Tyr Ser Gly Ser Glu Glu Glu Glu 320 325 330 Lys Asp Glu Thr Glu Tyr Glu Tyr Ser Gly Ser Glu Glu Glu Glu 320 325 330

Glu Glu Val Pro Glu Gln Glu Gly Glu Pro Ser Ser Ile Val Asn 335 340 345 Glu Glu Val Pro Glu Gln Glu Gly Glu Pro Ser Ser Ile Val Asn 335 340 345

Val Pro Gly Glu Ser Thr Leu Arg Arg Asp Phe Leu Arg Leu Gln 350 355 360 Val Pro Gly Glu Ser Thr Leu Arg Arg Asp Phe Leu Arg Leu Gln 350 355 360

Gln Glu Asn Lys Glu Arg Ser Glu Ala Leu Arg Arg Gln Gln Leu 365 370 375 Gln Glu Asn Lys Glu Arg Ser Glu Ala Leu Arg Arg Gln Gln Leu 365 370 375

Leu Gln Glu Gln Gln Leu Arg Glu Gln Glu Glu Tyr Lys Arg Gln 380 385 390 Leu Gln Glu Gln Gln Leu Arg Glu Gln Glu Glu Tyr Lys Arg Gln 380 385 390

Leu Leu Ala Glu Arg Gln Lys Arg Ile Glu Gln Gln Lys Glu Gln 395 400 405 Leu Leu Ala Glu Arg Gln Lys Arg Ile Glu Gln Gln Lys Glu Gln 395 400 405

Arg Arg Arg Leu Glu Glu Gln Gln Arg Arg Glu Arg Glu Ala Arg 410 415 420 Arg Arg Arg Leu Glu Glu Gln Gln Arg Arg Glu Arg Glu Ala Arg 410 415 420

Arg Gln Gln Glu Arg Glu Gln Arg Arg Arg Glu Gln Glu Glu Lys 425 430 435 Arg Gln Gln Glu Arg Glu Gln Arg Arg Arg Glu Gln Glu Glu Lys 425 430 435

Arg Arg Leu Glu Glu Leu Glu Arg Arg Arg Lys Glu Glu Glu Glu 440 445 450 Arg Arg Leu Glu Glu Leu Glu Arg Arg Arg Lys Glu Glu Glu Glu 440 445 450

Arg Arg Arg Ala Glu Glu Glu Lys Arg Arg Val Glu Arg Glu Gln 455 460 465 Arg Arg Arg Ala Glu Glu Glu Lys Arg Arg Val Glu Arg Glu Gln 455 460 465

Glu Tyr Ile Arg Arg Gln Leu Glu Glu Glu Gln Arg His Leu Glu 470 475 480 Glu Tyr Ile Arg Arg Gln Leu Glu Glu Glu Gln Arg His Leu Glu 470 475 480

Val Leu Gln Gln Gln Leu Leu Gln Glu Gln Ala Met Leu Leu His 485 490 495 Val Leu Gln Gln Gln Leu Leu Gln Glu Gln Wing Met Leu Leu His 485 490 495

Asp His Arg Arg Pro His Pro Gln His Ser Gln Gln Pro Pro Pro 500 505 510 Asp His Arg Arg Pro His Pro Gln His Ser Gln Gln Pro Pro Pro 500 505 510

Pro Gln Gln Glu Arg Ser Lys Pro Ser Phe His Ala Pro Glu Pro 515 520 525 Pro Gln Gln Glu Arg Ser Lys Pro Ser Phe His Ala Pro Glu Pro 515 520 525

Lys Ala His Tyr Glu Pro Ala Asp Arg Ala Arg Glu Val Pro Val 530 535 540 Lys Ala His Tyr Glu Pro Ala Asp Arg Ala Arg Glu Val Pro Val 530 535 540

Arg Thr Thr Ser Arg Ser Pro Val Leu Ser Arg Arg Asp Ser Pro 545 550 555 Arg Thr Thr Ser Arg Ser Pro Val Leu Ser Arg Arg Asp Ser Pro 545 550 555

Leu Gln Gly Ser Gly Gln Gln Asn Ser Gln Ala Gly Gln Arg Asn 560 565 570 Leu Gln Gly Ser Gly Gln Gln Asn Ser Gln Ala Gly Gln Arg Asn 560 565 570

Ser Thr Ser Ser Ile Glu Pro Arg Leu Leu Trp Glu Arg Val Glu 575 580 585 Ser Thr Ser Ser Ile Glu Pro Arg Leu Leu Trp Glu Arg Val Glu 575 580 585

Lys Leu Val Pro Arg Pro Gly Ser Gly Ser Ser Ser Gly Ser Ser 590 595 600 Lys Leu Val Pro Arg Pro Gly Be Gly Be Be Be Gly Be Be 590 595 600

Asn Ser Gly Ser Gln Pro Gly Ser His Pro Gly Ser Gln Ser Gly Asn Ser Gly Ser Gln Pro Gly Ser His Pro Gly Ser Gln Ser Gly

605 610 605 610

Ser Gly Glu Arg Phe Arg Val Arg Ser Ser Ser Lys Ser Glu Gly 620 625 630 Be Gly Glu Arg Phe Arg Val Arg Be Be Be Lys Be Glu Gly 620 625 630

Ser Pro Ser Gln Arg Leu Glu Asn Ala Val Lys Lys Pro Glu Asp 635 640 645 Ser Pro Ser Gln Arg Leu Glu Asn Ala Val Lys Lys Pro Glu Asp 635 640 645

Lys Lys Glu Val Phe Arg Pro Leu Lys Pro Ala Gly Glu Val Asp 650 655 660 Lys Lys Glu Val Phe Arg Pro Leu Lys Pro Wing Gly Glu Val Asp 650 655 660

Leu Thr Ala Leu Ala Lys Glu Leu Arg Ala Val Glu Asp Val Arg 665 670 675 Leu Thr Wing Leu Wing Lys Glu Leu Arg Wing Val Glu Asp Val Arg 665 670 675

Pro Pro His Lys Val Thr Asp Tyr Ser Ser Ser Ser Glu Glu Ser 680 685 690 Pro Pro His Lys Val Thr Asp Tyr Be Be Be Be Glu Glu Be 680 685 690

Gly Thr Thr Asp Glu Glu Asp Asp Asp Val Glu Gln Glu Gly Ala 695 700 705 Gly Thr Thr Asp Glu Glu Asp Asp Asp Val Glu Gln Glu Gly Ala 695 700 705

Asp Glu Ser Thr Ser Gly Pro Glu Asp Thr Arg Ala Ala Ser Ser 710 715 720 Asp Glu Ser Thr Ser Gly Pro Glu Asp Thr Arg Wing Be Ser 710 715 720

Leu Asn Leu Ser Asn Gly Glu Thr Glu Ser Val Lys Thr Met Ile 725 730 735 Leu Asn Leu Ser Asn Gly Glu Thr Glu Ser Val Lys Thr Met Ile 725 730 735

Val His Asp Asp Val Glu Ser Glu Pro Ala Met Thr Pro Ser Lys 740 745 750 Val His Asp Asp Val Glu Ser Glu Pro Wing Met Thr Pro Ser Lys 740 745 750

Glu Gly Thr Leu Ile Val Arg Gln Thr Gln Ser Ala Ser Ser Thr 755 760 765 Glu Gly Thr Leu Ile Val Arg Gln Thr Gln Ser Ala Ser Ser Thr 755 760 765

Leu Gln Lys His Lys Ser Ser Ser Ser Phe Thr Pro Phe Ile Asp 770 775 780 Leu Gln Lys His Lys Be Be Be Be Phe Thr Pro Phe Ile Asp 770 775 780

Pro Arg Leu Leu Gln Ile Ser Pro Ser Ser Gly Thr Thr Val Thr 785 790 795 Pro Arg Leu Leu Gln Ile Ser Pro Ser Ser Gly Thr Thr Val Thr 785 790 795

Ser Val Val Gly Phe Ser Cys Asp Gly Met Arg Pro Glu Ala Ile 800 805 810 Ser Val Val Gly Phe Ser Cys Asp Gly Met Arg Pro Glu Ala Ile 800 805 810

Arg Gln Asp Pro Thr Arg Lys Gly Ser Val Val Asn Val Asn Pro 815 820 825 Arg Gln Asp Pro Thr Arg Lys Gly Ser Val Val Asn Val Asn Pro 815 820 825

Thr Asn Thr Arg Pro Gln Ser Asp Thr Pro Glu Ile Arg Lys Tyr 830 835 840 Thr Asn Thr Arg Pro Gln Ser Asp Thr Pro Glu Ile Arg Lys Tyr 830 835 840

Lys Lys Arg Phe Asn Ser Glu Ile Leu Cys Ala Ala Leu Trp Gly 845 850 855 Lys Lys Arg Phe Asn Ser Glu Ile Leu Cys Wing Wing Leu Trp Gly 845 850 855

Val Asn Leu Leu Val Gly Thr Glu Ser Gly Leu Met Leu Leu Asp 860 865 870 Val Asn Leu Leu Val Gly Thr Glu Ser Gly Leu Met Leu Leu Asp 860 865 870

Arg Ser Gly Gln Gly Lys Val Tyr Pro Leu Ile Asn Arg Arg Arg 875 880 885 Arg Ser Gly Gln Gly Lys Val Tyr Pro Leu Ile Asn Arg Arg Arg 875 880 885

Phe Gln Gln Met Asp Val Leu Glu Gly Leu Asn Val Leu Val Thr 890 895 900 Phe Gln Gln Met Asp Val Leu Glu Gly Leu Asn Val Leu Val Thr 890 895 900

Ile Ser Gly Lys Lys Asp Lys Leu Arg Val Tyr Tyr Leu Ser Trp 905 910 915 Ile Ser Gly Lys Lys Asp Lys Leu Arg Val Tyr Tyr Leu Ser Trp 905 910 915

Leu Arg Asn Lys Ile Leu His Asn Asp Pro Glu Val Glu Lys Lys 920 925 930 Leu Arg Asn Lys Ile Leu His Asn Asp Pro Glu Val Glu Lys Lys 920 925 930

Gln Gly Trp Thr Thr Val Gly Asp Leu Glu Gly Cys Val His Tyr 935 940 Gln Gly Trp Thr Thr Val Gly Asp Leu Glu Gly Cys Val His Tyr 935 940

Lys Val Val Lys Tyr Glu Arg Ile Lys Phe Leu Val Ile Ala Leu 950 955 960 Lys Val Val Lys Tyr Glu Arg Ile Lys Phe Leu Val Ile Ala Leu 950 955 960

Lys Ser Ser Val Glu Val Tyr Ala Trp Ala Pro Lys Pro Tyr His 965 970 975 Lys Ser Ser Val Glu Val Tyr Wing Trp Wing Pro Lys Pro Tyr His 965 970 975

Lys Phe Met Ala Phe Lys Ser Phe Gly Glu Leu Val His Lys Pro 980 985 990 Lys Phe Met Ala Phe Lys Ser Phe Gly Glu Leu Val His Lys Pro 980 985 990

Leu Leu Val Asp Leu Thr Val Glu Glu Gly Gln Arg Leu Lys Val 995 1000 1005 Leu Leu Val Asp Leu Thr Val Glu Glu Gly Gln Arg Leu Lys Val 995 1000 1005

Ile Tyr Gly Ser Cys Ala Gly Phe His Ala Val Asp Val Asp Ser 1010 1015 1020 Ile Tyr Gly Ser Cys Ala Gly Phe His Ala Val Asp Val Asp Ser 1010 1015 1020

Gly Ser Val Tyr Asp Ile Tyr Leu Pro Thr His Val Arg Lys Asn 1025 1030 1035 Gly Ser Val Tyr Asp Ile Tyr Leu Pro Thr His Val Arg Lys Asn 1025 1030 1035

Pro His Ser Met Ile Gln Cys Ser Ile Lys Pro His Ala Ile Ile 1040 1045 1050 Pro His Ser Met Ile Gln Cys Ser Ile Lys Pro His Ala Ile Ile 1040 1045 1050

Ile Leu Pro Asn Thr Asp Gly Met Glu Leu Leu Val Cys Tyr Glu 1055 1060 1065 Ile Leu Pro Asn Thr Asp Gly Met Glu Leu Leu Val Cys Tyr Glu 1055 1060 1065

Asp Glu Gly Val Tyr Val Asn Thr Tyr Gly Arg Ile Thr Lys Asp 1070 1075 1080 Asp Glu Gly Val Tyr Val Asn Thr Tyr Gly Arg Ile Thr Lys Asp 1070 1075 1080

Val Val Leu Gln Trp Gly Glu Met Pro Thr Ser Val Ala Tyr Ile 1085 1090 1095 Val Val Leu Gln Trp Gly Glu Met Pro Thr Ser Val Ala Tyr Ile 1085 1090 1095

Arg Ser Asn Gln Thr Met Gly Trp Gly Glu Lys Ala Ile Glu Ile 1100 1105 1110 Arg Ser Asn Gln Thr Met Gly Trp Gly Glu Lys Ile Glu Ile 1100 1105 1110

Arg Ser Val Glu Thr Gly His Leu Asp Gly Val Phe Met His Lys 1115 1120 1125 Arg Ser Val Glu Thr Gly His Leu Asp Gly Val Phe Met His Lys 1115 1120 1125

Arg Ala Gln Arg Leu Lys Phe Leu Cys Glu Arg Asn Asp Lys Val 1130 1135 1140 Arg Wing Gln Arg Leu Lys Phe Leu Cys Glu Arg Asn Asp Lys Val 1130 1135 1140

Phe Phe Ala Ser Val Arg Ser Gly Gly Ser Ser Gln Val Tyr Phe 1145 1150 1155 Phe Phe Ala Ser Val Arg Be Gly Gly Ser Ser Gln Val Tyr Phe 1145 1150 1155

Met Thr Leu Gly Arg Thr Ser Leu Leu Ser Trp 1160 1165 Met Thr Leu Gly Arg Thr Ser Leu Leu Ser Trp 1160 1165

<210> 78 <210> 78

<211> 436 <211> 436

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 78 Met Arg Leu Ala Arg Leu Leu Arg Gly Ala Ala Leu Ala Gly Pro 1 5 10 15 <400> 78 Met Arg Leu Wing Arg Leu Leu Arg Gly Wing Wing Leu Wing Gly Pro 1 5 10 15

Gly Pro Gly Leu Arg Ala Ala Gly Phe Ser Arg Ser Phe Ser Ser 20 25 30 Gly Pro Gly Leu Arg Wing Gly Phe Be Arg Be Phe Be Be 20 25 30

Asp Ser Gly Ser Ser Pro Ala Ser Glu Arg Gly Val Pro Gly Gln 35 40 45 Asp Be Gly Be Be Pro Wing Be Glu Arg Gly Val Pro Gly Gln 35 40 45

Val Asp Phe Tyr Ala Arg Phe Ser Pro Ser Pro Leu Ser Met Lys 50 55 60 Val Asp Phe Tyr Ala Arg Phe Ser Pro Ser Pro Leu Ser Met Lys 50 55 60

Gln Phe Leu Asp Phe Gly Ser Val Asn Ala Cys Glu Lys Thr Ser 65 70 75 Gln Phe Leu Asp Phe Gly Ser Val Asn Ala Cys Glu Lys Thr Ser 65 70 75

Phe Met Phe Leu Arg Gln Glu Leu Pro Val Arg Leu Ala Asn Ile 80 85 90 Met Lys Glu Ile Ser Leu Leu Pro Asp Asn Leu Leu Arg Thr Pro 95 100 Phe Met Phe Leu Arg Gln Glu Leu Pro Val Arg Leu Wing Asn Ile 80 85 90 Met Lys Glu Ile Ser Leu Leu Pro Asp Asn Leu Leu Arg Thr Pro 95 100

Ser Val Gln Leu Val Gln Ser Trp Tyr Ile Gln Ser Leu Gln Glu 110 115 120 Ser Val Gln Leu Val Gln Ser Trp Tyr Ile Gln Ser Leu Gln Glu 110 115 120

Leu Leu Asp Phe Lys Asp Lys Ser Ala Glu Asp Ala Lys Ala Ile 125 130 135 Leu Leu Asp Phe Lys Asp Lys Ser Wing Glu Asp Wing Lys Ile Wing 125 130 135

Tyr Asp Phe Thr Asp Thr Val Ile Arg Ile Arg Asn Arg His Asn 140 145 150 Tyr Asp Phe Thr Asp Thr Val Ile Arg Ile Arg Asn Arg His Asn 140 145 150

Asp Val Ile Pro Thr Met Ala Gln Gly Val Ile Glu Tyr Lys Glu 155 160 165 Asp Val Ile Pro Thr Met Wing Gln Gly Val Ile Glu Tyr Lys Glu 155 160 165

Ser Phe Gly Val Asp Pro Val Thr Ser Gln Asn Val Gln Tyr Phe 170 175 180 Ser Phe Gly Val Asp Pro Val Thr Ser Gln Asn Val Gln Tyr Phe 170 175 180

Leu Asp Arg Phe Tyr Met Ser Arg Ile Ser Ile Arg Met Leu Leu 185 190 195 Leu Asp Arg Phe Tyr Met Ser Arg Ile Ser Ile Arg Met Leu Leu 185 190 195

Asn Gln His Ser Leu Leu Phe Gly Gly Lys Gly Lys Gly Ser Pro 200 205 210 Asn Gln His Ser Leu Leu Phe Gly Gly Lys Gly Lys Gly Ser Pro 200 205 210

Ser His Arg Lys His Ile Gly Ser Ile Asn Pro Asn Cys Asn Val 215 220 225 Ser His Arg Lys His Ile Gly Ser Ile Asn Pro Asn Cys Asn Val 215 220 225

Leu Glu Val Ile Lys Asp Gly Tyr Glu Asn Ala Arg Arg Leu Cys 230 235 240 Leu Glu Val Ile Lys Asp Gly Tyr Glu Asn Ala Arg Arg Leu Cys 230 235 240

Asp Leu Tyr Tyr Ile Asn Ser Pro Glu Leu Glu Leu Glu Glu Leu 245 250 255 Asp Leu Tyr Tyr Ile Asn Ser Pro Glu Leu Glu Leu Glu Glu Leu 245 250 255

Asn Ala Lys Ser Pro Gly Gln Pro Ile Gln Val Val Tyr Val Pro 260 265 270 Asn Ala Lys Ser Pro Gly Gln Pro Ile Gln Val Val Tyr Val Pro 260 265 270

Ser His Leu Tyr His Met Val Phe Glu Leu Phe Lys Asn Ala Met 275 280 285 Ser His Leu Tyr His Met Val Phe Glu Leu Phe Lys Asn Ala Met 275 280 285

Arg Ala Thr Met Glu His His Ala Asn Arg Gly Val Tyr Pro Pro 290 295 300 Arg Ala Thr Met Glu His His Ala Asn Arg Gly Val Tyr Pro Pro 290 295 300

Ile Gln Val His Val Thr Leu Gly Asn Glu Asp Leu Thr Val Lys 305 310 315 Ile Gln Val His Val Thr Leu Gly Asn Glu Asp Leu Thr Val Lys 305 310 315

Met Ser Asp Arg Gly Gly Gly Val Pro Leu Arg Lys Ile Asp Arg 320 325 330 Met Ser Asp Arg Gly Gly Gly Val Pro Leu Arg Lys Ile Asp Arg 320 325 330

Leu Phe Asn Tyr Met Tyr Ser Thr Ala Pro Arg Pro Arg Val Glu 335 340 345 Leu Phe Asn Tyr Met Tyr Ser Thr Ala Pro Arg Pro Arg Val Glu 335 340 345

Thr Ser Arg Ala Val Pro Leu Ala Gly Phe Gly Tyr Gly Leu Pro 350 355 360 Thr Ser Arg Wing Val Pro Leu Wing Gly Phe Gly Tyr Gly Leu Pro 350 355 360

Ile Ser Arg Leu Tyr Ala Gln Tyr Phe Gln Gly Asp Leu Lys Leu 365 370 375 Ile Ser Arg Leu Tyr Wing Gln Tyr Phe Gln Gly Asp Leu Lys Leu 365 370 375

Tyr Ser Leu Glu Gly Tyr Gly Thr Asp Ala Val Ile Tyr Ile Lys 380 385 390 Tyr Ser Leu Glu Gly Tyr Gly Thr Asp Ala Val Ile Tyr Ile Lys 380 385 390

Ala Leu Ser Thr Asp Ser Ile Glu Arg Leu Pro Val Tyr Asn Lys 395 400 405 Wing Leu Ser Thr Asp Ser Ile Glu Arg Leu Pro Val Tyr Asn Lys 395 400 405

Ala Ala Trp Lys His Tyr Asn Thr Asn His Glu Ala Asp Asp Trp 410 415 420 Wing Wing Trp Lys His Tyr Asn Thr Asn His Glu Wing Asp Asp Trp 410 415 420

Cys Val Pro Ser Arg Glu Pro Lys Asp Met Thr Thr Phe Arg Ser Cys Val Pro Ser Arg Glu Pro Lys Asp Met Thr Thr Phe Arg Ser

425 430 435 425 430 435

Ala To

<210> 79 <210> 79

<211> 928 <211> 928

<212> PRT <212> PRT

<213> Homo sapiens <213> Homo sapiens

<400> 79 Met Pro Pro Lys Thr Pro Arg Lys Thr Ala Ala Thr Ala Ala Ala 1 5 10 15 <400> 79 Met Pro Pro Lys Thr Pro Arg Lys Thr Wing Thr Wing Wing Wing 1 5 10 15

Ala Ala Val Asp Leu Asp Glu Met Ser Phe Thr Phe Thr Glu Leu 110 115 120 Wing Wing Val Asp Leu Asp Glu Met Ser Phe Thr Phe Thr Glu Leu 110 115 120

Gln Lys Asn Ile Glu Ile Ser Val His Lys Phe Phe Asn Leu Leu 125 130 135 Gln Lys Asn Ile Glu Ile Ser Val His Lys Phe Phe Asn Leu Leu 125 130 135

Phe Ile Lys Leu Ser Pro Pro Met Leu Leu Lys Glu Pro Tyr Lys 230 235 240 Phe Ile Lys Leu Ser Pro Pro Met Leu Leu Lys Glu Pro Tyr Lys 230 235 240

Thr Arg Ile Ile Glu Val Leu Cys Lys Glu His Glu Cys Asn Ile 275 280 285 Asp Glu Val Lys Asn Val Tyr Phe Lys Asn Phe Ile Pro Phe Met 290 295 Thr Arg Ile Ile Glu Val Leu Cys Lys Glu His Glu Cys Asn Ile 275 280 285 Asp Glu Val Lys Asn Val Tyr Phe Lys Asn Phe Ile Pro Phe Met 290 295

Leu Asp Ala Arg Leu Phe Leu Asp His Asp Lys Thr Leu Gln Thr 335 340 345 Leu Asp Wing Arg Leu Phe Leu Asp His Asp Lys Thr Leu Gln Thr 335 340 345

Asn Leu Asp Glu Glu Val Asn Val Ile Pro Pro His Thr Pro Val 365 370 375 Asn Leu Asp Glu Glu Val Asn Val Ile Pro Pro His Thr Pro Val 365 370 375

Arg Ile Met Glu Ser Leu Ala Trp Leu Ser Asp Ser Pro Leu Phe 560 565 570 Arg Ile Met Glu Ser Leu Wing Trp Leu Ser Asp Ser Pro Leu Phe 560 565 570

Asp Leu Ile Lys Gln Ser Lys Asp Arg Glu Gly Pro Thr Asp His 575 580 585 Asp Leu Ile Lys Gln Ser Lys Asp Arg Glu Gly Pro Thr Asp His 575 580 585

Lys Gly Ser Thr Thr Arg Val Asn Ser Thr Ala Asn Ala Glu Thr 620 625 Lys Gly Ser Thr Thr Arg Val Asn Ser Thr Ala Asn Ala Glu Thr 620 625

Gln Ala Thr Ser Ala Phe Gln Thr Gln Lys Pro Leu Lys Ser Thr 635 640 Gln Wing Thr Ser Wing Phe Gln Thr Gln Lys Pro Leu Lys Ser Thr 635 640

Leu Ala Glu Met Thr Ser Thr Arg Thr Arg Met Gln Lys Gln Lys 905 910 915 Leu Ala Glu Met Thr Ser Thr Arg Thr Arg Met Gln Lys Gln Lys 905 910 915

Claims

REIVINDICACIONES

1.one.: Método de clasificación de un tumor de carcinoma de pulmón de célula no pequeña en un mamífero, comprendiendo el método detectar la presencia de una variación de aminoácido en el dominio WD40 de FBXW7, o una variación de nucleótido en una región de un polinucleótido de FBXW7 que codifica el dominio WD40, en una muestra biológica derivada del mamífero, en el que la muestra biológica comprende células de carcinoma de pulmón de célula no pequeña. Classification method of a non-small cell lung carcinoma tumor in a mammal, the method comprising detecting the presence of an amino acid variation in the WD40 domain of FBXW7, or a nucleotide variation in a region of an FBXW7 polynucleotide that encodes the WD40 domain, in a biological sample derived from the mammal, in which the biological sample comprises non-small cell lung carcinoma cells.

2.2.: Método según la reivindicación 1, en el que se detecta el aminoácido. Method according to claim 1, wherein the amino acid is detected.

3.3.: Método según la reivindicación 2, en el que la variación de aminoácido es en una posición de aminoácido seleccionada entre G343, R399, e Y429. Method according to claim 2, wherein the amino acid variation is at an amino acid position selected from G343, R399, and Y429.

4.Four.: Método según la reivindicación 1, en el que se detecta la variación de nucleótido. Method according to claim 1, wherein the nucleotide variation is detected.

5.5.: Método según la reivindicación 4, en el que la variación de nucleótido es en una posición de nucleótido seleccionada entre C153607116, C153604971, y T153604881 del cromosoma 4, en el que dicha posición de nucleótido corresponde a la posición G113, G1292 o A1382 de SEC ID NO:5, respectivamente. Method according to claim 4, wherein the nucleotide variation is in a nucleotide position selected from C153607116, C153604971, and T153604881 of chromosome 4, wherein said nucleotide position corresponds to position G113, G1292 or A1382 of SEQ ID NO: 5, respectively.

6.6.: Método según la reivindicación 5, en el que la variación de nucleótido es un cambio de nucleótido seleccionado entre C153607116T, C153604971T, y T153604881A, en el que dicho cambio de nucleótido corresponde a G1123A, G1292A o A1382T de SEC ID NO:5, respectivamente. Method according to claim 5, wherein the nucleotide variation is a nucleotide change selected from C153607116T, C153604971T, and T153604881A, wherein said nucleotide change corresponds to G1123A, G1292A or A1382T of SEQ ID NO: 5, respectively.

7.7.: Método para predecir si un carcinoma de pulmón de célula no pequeña responderá a un agente terapéutico que reconoce FBXW7 o polinucleótido de FBXW77, comprendiendo el método determinar si el carcinoma de pulmón de célula no pequeña comprende una variación de aminoácido en el dominio WD40 de FBXW7, o una variación de nucleótido en una región de un polinucleótido de FBXW7 que codifica el dominio WD40, en el que la presencia de una variación de aminoácido o una variación de nucleótido indica que el carcinoma de pulmón de célula no pequeña responderá al agente terapéutico. Method for predicting whether a non-small cell lung carcinoma will respond to a therapeutic agent that recognizes FBXW7 or FBXW77 polynucleotide, the method comprising determining whether non-small cell lung carcinoma comprises an amino acid variation in the WD40 domain of FBXW7, or a nucleotide variation in a region of an FBXW7 polynucleotide encoding the WD40 domain, in which the presence of an amino acid variation or a nucleotide variation indicates that non-small cell lung carcinoma will respond to the therapeutic agent.

8.8.: Método según la reivindicación 7, en el que se detecta la variación de aminoácido en FBXW7. Method according to claim 7, wherein the amino acid variation in FBXW7 is detected.

9.9.: Método según la reivindicación 8, en el que la variación de aminoácido es en una posición de aminoácido seleccionada entre G343, R399, e Y429. Method according to claim 8, wherein the amino acid variation is at an amino acid position selected from G343, R399, and Y429.

10.10.: Método según la reivindicación 7, en el que se detecta la variación de nucleótido. Method according to claim 7, wherein the nucleotide variation is detected.

11.eleven.: Método según la reivindicación 10, en el que la variación de nucleótido es en una posición de nucleótido seleccionada entre C153607116, C153604971, y T153604881 del cromosoma 4, en el que dicha posición de nucleótido corresponde a la posición G113, G1292 o A1382 de la SEC ID NO:5, respectivamente. Method according to claim 10, wherein the nucleotide variation is in a nucleotide position selected from C153607116, C153604971, and T153604881 of chromosome 4, wherein said nucleotide position corresponds to position G113, G1292 or A1382 of the SEC ID NO: 5, respectively.

12.12.: Método según la reivindicación 11, en el que la variación de nucleótido es un cambio de nucleótido seleccionado entre C153607116T, C153604971T, y T153604881A, en el que dicho cambio de nucleótido corresponde a G1123A, G1292A o A1382T de la SEC ID NO:5, respectivamente. Method according to claim 11, wherein the nucleotide variation is a nucleotide change selected from C153607116T, C153604971T, and T153604881A, wherein said nucleotide change corresponds to G1123A, G1292A or A1382T of SEQ ID NO: 5, respectively .